The 2002 Official Patient's Sourcebook on Fragile X Syndrome

THE 2002 OFFICIAL PARENT’S SOURCEBOOK

on

RAGILE YNDROME J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your child’s physician. All matters regarding your child’s health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before administering any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The 2002 Official Parent’s Sourcebook on Fragile X Syndrome: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83201-3 1. Fragile X Syndrome-Popular works.I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for parent use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of fragile X syndrome.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to fragile X syndrome. All of the Official Parent’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Parent’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Parent’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to fragile X syndrome, Official Parent’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Down Syndrome

·

The Official Patient's Sourcebook on Infantile Apnea

·

The Official Patient's Sourcebook on Klinefelter Syndrome

·

The Official Patient's Sourcebook on Mccune Albright Syndrome

·

The Official Patient's Sourcebook on Phenylketonuria

·

The Official Patient's Sourcebook on Pituitary Tumors

·

The Official Patient's Sourcebook on Primary Immunodeficiency

·

The Official Patient's Sourcebook on Sudden Infant Death Syndrome

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION ................................................................................................................................. 1 Overview ....................................................................................................................................... 1 Organization ................................................................................................................................. 3 Scope.............................................................................................................................................. 3 Moving Forward............................................................................................................................ 4 PART I: THE ESSENTIALS ............................................................................................................. 7 CHAPTER 1. THE ESSENTIALS ON FRAGILE X SYNDROME: GUIDELINES ......................................... 9 Overview ....................................................................................................................................... 9 What Is Fragile X Syndrome? ..................................................................................................... 10 Inheritance................................................................................................................................... 12 Testing for Fragile X Carrier....................................................................................................... 13 Prenatal Testing .......................................................................................................................... 13 Diagnosing and Treating Fragile X Syndrome ........................................................................... 13 Medical Problems ........................................................................................................................ 16 Education of Children with Fragile X ......................................................................................... 16 Additional Therapies ................................................................................................................... 17 Future Research........................................................................................................................... 17 More Guideline Sources .............................................................................................................. 18 Vocabulary Builder...................................................................................................................... 22 CHAPTER 2. SEEKING GUIDANCE ................................................................................................... 25 Overview ..................................................................................................................................... 25 Associations and Fragile X Syndrome ........................................................................................ 25 Finding More Associations ......................................................................................................... 30 Finding Doctors........................................................................................................................... 32 Finding a Pediatrician ................................................................................................................. 33 Selecting Your Doctor ................................................................................................................. 33 Working with Your Child’s Doctor ............................................................................................. 34 Broader Health-Related Resources .............................................................................................. 35 Vocabulary Builder...................................................................................................................... 35 PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL ........................... 37 CHAPTER 3. STUDIES ON FRAGILE X SYNDROME........................................................................... 39 Overview ..................................................................................................................................... 39 The Combined Health Information Database .............................................................................. 39 Federally-Funded Research on Fragile X Syndrome ................................................................... 42 E-Journals: PubMed Central ....................................................................................................... 56 The National Library of Medicine: PubMed................................................................................ 57 Vocabulary Builder...................................................................................................................... 58 CHAPTER 4. PATENTS ON FRAGILE X SYNDROME ......................................................................... 61 Overview ..................................................................................................................................... 61 Patents on Fragile X Syndrome................................................................................................... 62 Patent Applications on Fragile X Syndrome............................................................................... 65 Keeping Current .......................................................................................................................... 65 Vocabulary Builder...................................................................................................................... 65 CHAPTER 5. BOOKS ON FRAGILE X SYNDROME ............................................................................. 67 Overview ..................................................................................................................................... 67 Book Summaries: Federal Agencies ............................................................................................. 68 Book Summaries: Online Booksellers .......................................................................................... 71 The National Library of Medicine Book Index............................................................................. 73 Chapters on Fragile X Syndrome ................................................................................................ 76

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General Home References ............................................................................................................ 79 Vocabulary Builder...................................................................................................................... 80 CHAPTER 6. MULTIMEDIA ON FRAGILE X SYNDROME .................................................................. 83 Overview ..................................................................................................................................... 83 Bibliography: Multimedia on Fragile X Syndrome ..................................................................... 83 Vocabulary Builder...................................................................................................................... 84 CHAPTER 7. PERIODICALS AND NEWS ON FRAGILE X SYNDROME ............................................... 85 Overview ..................................................................................................................................... 85 News Services & Press Releases .................................................................................................. 85 Newsletters on Fragile X Syndrome............................................................................................ 88 Academic Periodicals covering Fragile X Syndrome................................................................... 89 Vocabulary Builder...................................................................................................................... 90 CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES ................................................................ 91 Overview ..................................................................................................................................... 91 NIH Guidelines ........................................................................................................................... 91 NIH Databases ............................................................................................................................ 92 Other Commercial Databases ...................................................................................................... 97 The Genome Project and Fragile X Syndrome ............................................................................ 97 Specialized References ............................................................................................................... 102 CHAPTER 9. DISSERTATIONS ON FRAGILE X SYNDROME ............................................................ 103 Overview ................................................................................................................................... 103 Dissertations on Fragile X Syndrome ....................................................................................... 103 Keeping Current ........................................................................................................................ 104 PART III. APPENDICES .............................................................................................................. 105 APPENDIX A. RESEARCHING YOUR CHILD’S MEDICATIONS....................................................... 107 Overview ................................................................................................................................... 107 Your Child’s Medications: The Basics....................................................................................... 108 Learning More about Your Child’s Medications....................................................................... 109 Commercial Databases............................................................................................................... 110 Contraindications and Interactions (Hidden Dangers)............................................................. 111 A Final Warning ....................................................................................................................... 112 General References..................................................................................................................... 113 APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ............................................................... 115 Overview ................................................................................................................................... 115 What Is CAM? .......................................................................................................................... 116 What Are the Domains of Alternative Medicine? ..................................................................... 116 Can Alternatives Affect My Child’s Treatment? ...................................................................... 120 Finding CAM References on Fragile X Syndrome.................................................................... 120 Additional Web Resources......................................................................................................... 123 General References..................................................................................................................... 124 Vocabulary Builder.................................................................................................................... 125 APPENDIX C. RESEARCHING NUTRITION..................................................................................... 127 Overview ................................................................................................................................... 127 Food and Nutrition: General Principles .................................................................................... 128 Finding Studies on Fragile X Syndrome ................................................................................... 132 Federal Resources on Nutrition................................................................................................. 133 Additional Web Resources......................................................................................................... 134 Vocabulary Builder.................................................................................................................... 135 APPENDIX D. FINDING MEDICAL LIBRARIES ............................................................................... 137 Overview ................................................................................................................................... 137 Preparation ................................................................................................................................ 137 Finding a Local Medical Library ............................................................................................... 138 Medical Libraries Open to the Public ........................................................................................ 138

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APPENDIX E. YOUR CHILD’S RIGHTS AND INSURANCE............................................................... 145 Overview ................................................................................................................................... 145 Your Child’s Rights as a Patient ............................................................................................... 145 Parent Responsibilities .............................................................................................................. 149 Choosing an Insurance Plan...................................................................................................... 150 Medicaid .................................................................................................................................... 152 NORD’s Medication Assistance Programs............................................................................... 153 Additional Resources................................................................................................................. 153 ONLINE GLOSSARIES ............................................................................................................... 155 Online Dictionary Directories................................................................................................... 158 FRAGILE X SYNDROME GLOSSARY..................................................................................... 159 General Dictionaries and Glossaries ......................................................................................... 168 INDEX.............................................................................................................................................. 170

Introduction

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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that all parents incorporate education into the treatment process. According to the AHRQ: Finding out more about your [child’s] condition is a good place to start. By contacting groups that support your [child’s] condition, visiting your local library, and searching on the Internet, you can find good information to help guide your decisions for your [child’s] treatment. Some information may be hard to find—especially if you don't know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist parents in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3 Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

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Fragile X Syndrome

Since the late 1990s, physicians have seen a general increase in parent Internet usage rates. Parents frequently enter their children’s doctor's offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding children through sound therapies. The 2002 Official Parent’s Sourcebook on Fragile X Syndrome has been created for parents who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to fragile X syndrome, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on fragile X syndrome. Given parents’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on fragile X syndrome should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your child’s best option. This sourcebook is no exception. Each child is unique. Deciding on

Introduction

3

appropriate options is always up to parents in consultation with their children’s physicians and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching fragile X syndrome (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other parent networks dedicated to fragile X syndrome. It also gives you sources of information that can help you find a doctor in your local area specializing in treating fragile X syndrome. Collectively, the material presented in Part I is a complete primer on basic research topics for fragile X syndrome. Part II moves on to advanced research dedicated to fragile X syndrome. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on fragile X syndrome. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading covering fragile X syndrome or related disorders. The appendices are dedicated to more pragmatic issues facing parents. Accessing materials via medical libraries may be the only option for some parents, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing children with fragile X syndrome and their families.

Scope While this sourcebook covers fragile X syndrome, doctors, research publications, and specialists may refer to your child’s condition using a variety of terms. Therefore, you should understand that fragile X syndrome is often considered a synonym or a condition closely related to the following: ·

Fraxa

·

Marker X Syndrome

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Fragile X Syndrome

·

Martin-bell Syndrome

·

X-linked Mental Retardation

·

X-linked Mental Retardation and Macroorchidism

In addition to synonyms and related conditions, physicians may refer to fragile X syndrome using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world's illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for fragile X syndrome:4 ·

758.9 conditions due to anomaly of unspecified chromosome

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to fragile X syndrome. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by parents, patients, or their family members. These generally take a layperson's approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful.

This list is based on the official version of the World Health Organization's 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.” 4

Introduction

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As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian.

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PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on fragile X syndrome. The essentials typically include a definition or description of the condition, a discussion of who it affects, the signs or symptoms, tests or diagnostic procedures, and treatments for disease. Your child’s doctor or healthcare provider may have already explained the essentials of fragile X syndrome to you or even given you a pamphlet or brochure describing the condition. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what the doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

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CHAPTER 1. THE ESSENTIALS ON FRAGILE X SYNDROME: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on fragile X syndrome. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the parent in mind. Since new guidelines on fragile X syndrome can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current guidelines and fact sheets on fragile X syndrome. Originally founded in 1887, the NIH is one of the world's foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world's most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Fragile X Syndrome

There is no guarantee that any one Institute will have a guideline on a specific medical condition, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare disorders. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with fragile X syndrome and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

Among those listed above, the National Institute of Child Health and Human Development (NICHD) is especially noteworthy. The mission of the NICHD, a part of the National Institutes of Health (NIH), is to support and conduct research on topics related to the health of children, adults, families, and populations. NICHD research focuses on the idea that events that happen prior to and throughout pregnancy as well as during childhood have a great impact on the health and well-being of adults. The following guideline is one the NICHD provides concerning fragile X syndrome.6

What Is Fragile X Syndrome?7 Fragile X syndrome is the most common genetically-inherited form of mental retardation currently known. In addition to intellectual disability, some individuals with Fragile X display common physical traits and characteristic facial features, such as prominent ears. Children with Fragile X often appear normal in infancy but develop typical physical characteristics during their lifetime. Mental impairment may range from mild learning disability and hyperactivity to severe mental retardation and autism. This genetic syndrome is caused by a defect on the X chromosome. Because of scientific advances, improvements in genetic testing, and increased awareness, the 6 This and other passages have been adapted from the NIH and NICHD: http://www.nichd.nih.gov/default.htm. “Adapted” signifies that the text has been reproduced with attribution, with some or no editorial adjustments. 7 Adapted from the National Institute of Child Health and Human Development (NICHD): http://www.nichd.nih.gov/publications/pubs/fragilextoc.htm.

Guidelines 11

number of children diagnosed with Fragile X has increased significantly over the last decade. A substantial research effort led to the 1991 discovery of FMR-1 (Fragile X mental retardation), the gene that when damaged causes Fragile X. Although the normal function of the FMR-1 gene is not fully understood, it appears to be important early in development. The mechanism by which the normal FMR-1 gene is converted into an altered, or mutant, gene capable of causing disease symptoms involves an increase in the length of the gene. A small region of the gene, CGG, undergoes repeated duplications, forming deoxyribonucleic acid (DNA) repeats that result in a longer gene. The lengthened DNA region is susceptible to a chemical modification process called DNA methylation. When the number of repeats is small (less than 200) the individual often has no signs of the disorder. However, in individuals with a larger number of repeats, the characteristics that are typical of Fragile X are observed. In families that exhibit Fragile X, both the number of repeats and the length of the chromosome increase with succeeding generations. The severity of the symptoms increases with the increasing length of the repeated region. Fragile X exhibits X-linkage. The effect of X-linkage is that the frequency of the syndrome is greater in males than in females. To understand the mechanism of X-linkage some background information on the organization of human chromosomes is needed. Human females typically have two X chromosomes, and human males have one X and one Y chromosome. A female who inherits a chromosome carrying the Fragile X gene from either parent is likely to inherit a normal X chromosome from the other parent. The normal X chromosome could provide the normal gene function and mask the presence of the Fragile X gene in a female. In that case, the female would still possess the Fragile X gene and be capable of passing it on to her offspring, but she would not exhibit symptoms. She would be a “carrier.” On the other hand, a male who inherits the Fragile X gene from his mother would inherit a Y chromosome and not a normal X chromosome from his father, and therefore a male with one copy of the gene is likely to show symptoms. We do not yet have a complete understanding of the mechanism of genetic transmission of Fragile X. For example, it is not known why approximately one-fifth of males who carry mutated forms of FMR-1 are either unaffected or only mildly affected. In some cases, a single copy of the Fragile X gene is sufficient to cause the syndrome in females. The situation is made more complex by the fact that the intensity of the symptoms increases with succeeding generations. The observable characteristics of Fragile X occur in approximately 1 in 1,000 male births and 1 in 2,500 female births.

12 Fragile X Syndrome

On a normal X chromosome, the FMR-1 region of the chromosome contains 50 or fewer copies of the CGG repeat. This same region may be repeated hundreds or even thousands of times in individuals with Fragile X. Researchers have made a surprising correlation between the number of DNA repeats and the degree of clinical impairment. Individuals with between 50 and 200 repeats are often carriers of Fragile X who have mild symptoms or no symptoms at all. When the number of repeats increases, the chemical modification process called DNA methylation is more likely to occur. It is this chemical modification that appears to inactivate the FMR-1 gene, leading to deficits in cognitive processing. Why methylation of this region of DNA leads to the symptoms of Fragile X is not understood. Mental impairment in Fragile X appears to correlate with DNA containing more than 200 repeats. In that case, most males are impaired and 50 percent of females show some learning disabilities. However, there are exceptions, including individuals with enormous numbers of repeats who have no apparent impairment.

Inheritance In normal individuals the FMR-1 gene is passed on, in stable fashion, from the parent to the offspring. In Fragile X individuals, the repeated sequences not only expand abnormally, but are unstable and the degree of impairment in offspring may vary. The Fragile X mutation appears to increase in length as it is inherited by succeeding generations. This phenomenon is known as “genetic anticipation.” Eventually, the mutation reaches a critical number of repeats and causes Fragile X syndrome. For example, a male may have normal IQ, no Fragile X symptoms, and a short region of DNA repeats at the Fragile X region of his X chromosome. This individual, called a “transmitting” male, may have a daughter with 50 to 200 repeats. At that stage the condition is considered a “premutation,” as there still may be no apparent symptoms. This daughter, a “carrier,” might have a son with 1,000 repeats and the full blown Fragile X syndrome. If a woman is a carrier, each of her children has a 50 percent chance of inheriting her Fragile X gene. Each time her Fragile X gene is inherited, it is likely to have expanded in length. A daughter who inherits the gene will be a carrier with some chance of impairment; a son who inherits the gene has an 80 percent likelihood of developing Fragile X syndrome.

Guidelines 13

Testing for Fragile X Carrier A simple test is now available that can determine if a woman is carrier of the Fragile X gene. A drop of blood can be taken from the woman's finger and analyzed quickly and inexpensively. If a woman who is found to be a carrier is pregnant, she can arrange for testing of the fetus, as described below. For a woman with a family history of retardation, testing before pregnancy will help determine if she is at risk.

Prenatal Testing Three prenatal tests can determine if Fragile X is present in the fetus. Chorionic villi sampling (CVS) involves extracting a tiny amount of fetal tissue at 9 to 11 weeks of pregnancy. CVS is not widely used and carries a 1-2 percent risk of miscarriage following the procedure. Amniocentesis is the removal and analysis of a small sample of fetal cells from the amniotic fluid. Amniocentesis is widely available and involves a lower risk of miscarriage. However, amniocentesis cannot be done until the 15th to 18th week of pregnancy and it usually takes an additional 2 to 4 weeks for the cells to grow and be analyzed. So a woman may have to wait until the 17th to 22nd week of her pregnancy to have the results of this test. The third method, percutaneous umbilical blood sampling (PUBS), is the most accurate method and can be used to confirm the results of CVS or amniocentesis. However, PUBS is not widely available, PUBS is not done until the 18th to 22nd week and carries the greatest risk of miscarriage.

Diagnosing and Treating Fragile X Syndrome Individuals with Fragile X may have a cluster of physical, behavioral, mental, and other characteristics. These symptoms may vary in number and degree among affected children. In the best of circumstances, early identification of a child with Fragile X and subsequent treatment involves a team of professionals. These might include a speech and language pathologist, an occupational therapist (perhaps even a specialist in sensory integration), a physical therapist, a special education teacher, a genetics counselor, and a psychologist.

14 Fragile X Syndrome

Physical Characteristics Males with Fragile X have some common physical characteristics: a long narrow face; large or prominent ears; and macroorchidism (enlarged testicles). More than 80 percent of males with Fragile X develop at least one of these features, but often not until after puberty. Other physical characteristics of males with Fragile X are double-jointed fingers, flat feet, puffy eyelids, and “hollow chest.” These physical features may indicate an underlying abnormality of the connective tissue, although no specific connective tissue defect has been detected. Females with Fragile X syndrome do not exhibit most of the physical characteristics found in males with Fragile X, although they often have large or prominent ears.

Behavioral Characteristics The most prevalent behavioral characteristics of children with Fragile X are attention problems and hyperactivity, known as attention-deficit hyperactivity disorder (ADHD). ADHD is frequently treated with medication, generally central nervous system stimulants such as methylphenidate (Ritalin®), pemoline (Cylert®) and dextroamphetamine (Dexedrine®). Because these drugs have side effects that include irritability and poor appetite, alternatives such as amantadine and clonidine may be appropriate. Amantadine has been used with surprising success to treat hyperactivity and attention difficulties in children with low IQs, for whom stimulants are generally less effective. Fragile X children with ADHD may benefit from the addition of tricyclic antidepressants or a major tranquilizer such as thioridazine (Mellaril®). Because mood swings and temper tantrums present major difficulties for children with Fragile X, psychotherapeutic medications such as Lithium and more recently fluoxetine (Prozac®) have helped control aggression and outbursts. Anticonvulsants such as carbamazepine or valproate, used if seizures are present, can also help treat behavior problems, including aggression in males with Fragile X. Children with Fragile X have strong reactions to changes in their environment, and their heightened anxiety can compound their behavioral difficulties. They appear to have an underlying disability related to processing external stimuli, called sensory integration (see Additional Therapies). Extreme hypersensitivity to their environment makes is difficult

Guidelines 15

for them to screen out stimuli such as noise, lights, or odors. This, in turn, often provokes emotional outbursts or tantrums. Some of the other behaviors associated with Fragile X are similar to those of autism, including hand flapping, hand biting, poor eye contact, and tactile defensiveness (responding negatively to being touched). However, one strength of males with Fragile X is their great sociability and friendliness, in contrast to autistic children, who appear unable to relate to others. Researchers recommend that autistic children be screened for Fragile X.

Mental Impairment Mental retardation associated with Fragile X is similar to that of Down syndrome in that most of those affected fall somewhere in the middle range of impairment. There are differences between males and females with Fragile X with respect to their mental impairment. There are differences between males and females with Fragile X with respect to their mental impairment. Many females with Fragile X syndrome are learning disabled in math, but perform exceptionally well in reading and spelling. In addition, one-third of females with Fragile X have metal disabilities similar to those associated with schizophrenia, such as dependence on odd forms of communication and preference for social isolation. Males with Fragile X appear to differ in mental development from both females with Fragile X and children with other kinds of developmental delays who exhibit learning disabilities. Males with Fragile X may actually achieve more than some other developmentally disabled children with higher IQ scores. It is important for educators to understand the particular difficulties of males with Fragile X. They appear to process information in simultaneous fashion; this causes difficulty when they are taught skills that require sequential processing of information, such as reading. For males with Fragile X, learning often involves seeing the whole in order to understand the parts.

Speech, Language, and Learning Disabilities Speech and language present special difficulties. Children with Fragile X often speak in rapid bursts or repeat words (called echolalia). For males with Fragile X, the primary language difficulty is perseveration. Perseveration is the inability to complete a sentence because of continuous repetition of words at the end of a phrase. Another language-based behavior displayed by males with Fragile X is talking inappropriately and incessantly about one

16 Fragile X Syndrome

topic. This particular difficulty distinguishes males with Fragile X from individuals with other forms of mental retardation or autism. Speech problems are made worse in situations where the child must have eye contact with another person or when the child becomes anxious, leading researchers to suspect some underlying relationship between difficulties with language and difficulties with sensory processing.

Medical Problems Although most children with Fragile X do not have serious physical problems, they are at greater risk for certain types of moderate medical problems than are normal children. For example, they often suffer recurrent otitis media (inner ear infections), which should be treated as early as possible to prevent it from becoming a source of language difficulties. Common eye problems include myopia (nearsightedness) and a high incidence of “lazy eye.” Orthopedic difficulties related to flat feet and joint laxity may occur. Twenty percent of males with Fragile X are prone to seizures, including petit mal, grand mal, and temporal lobe seizures. In addition, many children with Fragile X have digestive disorders, such as gastroesophageal reflux, that causes gagging, regurgitation, and discomfort.

Education of Children with Fragile X Even at a young age, children with Fragile X tend to be good at imitation and to be very social. Consequently, they can benefit immensely from early intervention programs and prolonged contact with children who are developing normally. Congressional legislation (Public Law 99-457) mandates early intervention services for children with developmental delays, ages 3 to 5 years; in some states this includes younger children. (For help finding local programs see Sources of Information section.) Parents and educators should be aware that many children with Fragile X achieve above the level that would have been predicted from measured IQ, and it is important for parents and educators to help these children reach their maximum potential. Children with Fragile X with an IQ above 70 generally do best when mainstreamed into a well-organized classroom environment with individualized help from special education experts and other professionals. Cooperative instruction, using peers to help teach, often relieves some of the stress of the classroom environment and the teacherchild relationship.

Guidelines 17

Additional Therapies To counter the sensory integration difficulties of children with Fragile X, a wide range of strategies has been employed. Minimizing exposure to noise and odors may prevent overstimulation. Therapeutic calming techniques, such as music therapy, can also be used. It may be helpful to make special efforts to provide structure in the immediate environment and in day-to-day activities. Children with Fragile X often develop their own routines. Occupational therapists specializing in sensory integration therapy can work with children with Fragile X to help them organize environmental stimuli and to improve their response to formal education. The strength of their visual memory means that children with Fragile X process information better when they are presented with whole pictures rather than when information is presented orally or sequentially, as in normal reading. As a result, use of pictures, message boards, calculators, and other visual devices may be helpful. Some children with Fragile X learn sign language, a visual system. Computer software is now available for learning basic concepts in language and math using high-interest visual themes. Psychology professionals warn against the tendency to assume that all characteristics of a child with Fragile X stem directly from the Fragile X syndrome. The emotional difficulties of an individual with Fragile X may include insecurity and anxiety related to having a disability. These strategies are only a few that specialists have developed to help children with Fragile X. Parents and other individuals working with these children should make use of their assets, such as their positive outlook on life and love of other people. Children with Fragile X should be encouraged to express their feelings openly even when they have difficulty using words.

Future Research Since the discovery of the Fragile X gene in 1991, there has been tremendous progress in the understanding of this disorder. Preimplantation genetic screening, using molecular genetic screening of in vitro fertilized embryos followed by implantation of embryos that are free of the disorder, may be available to would-be parents in the near future. Some affected families argue that not enough research is being conducted on the treatment of Fragile X. In response, experts explain that it is difficult to

18 Fragile X Syndrome

treat Fragile X without first understanding more about the biology of the condition and the meaning of the DNA expansions. It has been particularly difficult to investigate these questions in the absence of an animal model. The nature of the Fragile X mutation may itself be a source of the difficulty scientists are having in developing an animal model of the disease. The excess genetic material of the Fragile X defect is so voluminous and so fragile that inserting the Fragile X DNA into animal cells has been a problem for laboratory scientists. However, there has been some recent progress in this area, and continued research is likely to bring success. Once an animal model is developed, researchers will be able to learn more about the basis of the Fragile X mutation and the mechanisms that contribute to its unstable character. Ongoing analysis of the FMR-1 gene and its protein product may help researchers understand the normal function of this protein and perhaps find a way to intervene when its functioning goes awry.

More Guideline Sources The guideline above on fragile X syndrome is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to fragile X syndrome. Many of the guidelines listed below address topics that may be of particular relevance to your child’s specific situation, while certain guidelines will apply to only some children with fragile X syndrome. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

Topic Pages: MEDLINEplus For parents wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and parentoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas.

Guidelines 19

If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly parent-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and educational guidelines on fragile X syndrome and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

Facts About Fragile X Syndrome Source: Bethesda, MD: National Institutes of Child Health and Human Development, National Institutes of Health (NIH). April 1996. 15 p. Contact: Available from National Institutes of Child Health and Human Development (NICHD). National Institutes of Health (NIH), 31 Center Drive, Room 2A32, MSC2425, Bethesda, MD 20892-2425. Price: Single copy free. NIH Publication Number 96-3402. Summary: This brochure describes Fragile X syndrome, the most common genetically-inherited form of mental retardation currently known. In addition to intellectual disability, some individuals with Fragile X display common physical traits and characteristic facial features, such as prominent ears. Mental impairment may range from mild learning disability and hyperactivity to severe mental retardation and autism. The brochure describes Fragile X and the research effort that led to the 1991 discovery of the gene (FMR-1) that, when damaged, causes Fragile X. The brochure then discusses inheritance, testing for the Fragile X gene, prenatal tests, diagnosis and treatment, physical disabilities associated with Fragile X, speech language and learning disabilities associated with Fragile X, medical problems, educational considerations, and future research strategies. In discussing

20 Fragile X Syndrome

accommodations for children with Fragile X, the brochure notes that to counter the sensory integration difficulties often present, techniques such as minimizing exposure to noise and odors may prevent overstimulation. Therapeutic calming techniques, such as music therapy, may also be useful. Many children with Fragile X achieve above the level that would have been predicted from measured IQ; it is important for parents and educators to help these children reach their maximum potential. The brochure includes a brief description of two resource organizations, the National Fragile X Foundation and the FRAXA Research Foundation, Inc.; the contact information for both is included. ·

FRAXA Research Foundation: Supporting Research for the Treatment of Fragile X Syndrome Source: West Newbury, MA: FRAXA Research Foundation, Inc. 1994. Contact: Available from FRAXA Research Foundation, Inc. P.O. Box 935, West Newbury, MA 01985. (508) 462-1990. Price: Free. Summary: This brochure presents general information about fragile X syndrome, a common inherited cause of mental retardation. Characteristics and symptoms of fragile X syndrome, its causes, and treatment are discussed. The goals and services of the FRAXA Research Foundation also are briefly described.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “fragile X syndrome” or synonyms. The following was recently posted: ·

Genetic counseling for fragile X syndrome: recommendations of the National Society of Genetic Counselors. Source: National Society of Genetic Counselors.; 2000; 23 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1772&sSearch_string=fragile+X+syndrome Healthfinder™

Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that

Guidelines 21

contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·

Facts About Fragile X Syndrome Summary: This document discusses the scientific advances and improvements in genetic testing, and increased awareness of fragile X syndrome over the last decade. Source: National Institute of Child Health and Human Development, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2008

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to fragile X syndrome. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and parents. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than parents, you can view the current list of conditions covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm.

22 Fragile X Syndrome

Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

·

Med Help International: http://www.medhelp.org/HealthTopics/A.html

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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: An agent that stimulates the mood of a depressed patient, including tricyclic antidepressants and monoamine oxidase inhibitors. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness,

Guidelines 23

and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Embryo: In animals, those derivatives of the fertilized ovum that eventually become the offspring, during their period of most rapid development, i.e., after the long axis appears until all major structures are represented. In man, the developing organism is an embryo from about two weeks after fertilization to the end of seventh or eighth week. [EU] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU] Lithium: Lithium. An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH] Lobe: A more or less well-defined portion of any organ, especially of the brain, lungs, and glands. Lobes are demarcated by fissures, sulci, connective tissue, and by their shape. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU]

24 Fragile X Syndrome

Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Reflux: A backward or return flow. [EU] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, hallucinations, emotional disharmony, and regressive behavior. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder." [NIH] Stimulant: 1. producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. an agent or remedy that produces stimulation. [EU] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU]

Seeking Guidance 25

CHAPTER 2. SEEKING GUIDANCE Overview Some parents are comforted by the knowledge that a number of organizations dedicate their resources to helping people with fragile X syndrome. These associations can become invaluable sources of information and advice. Many associations offer parent support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.8 In addition to support groups, your child’s physician can be a valuable source of guidance and support. In this chapter, we direct you to resources that can help you find parent organizations and medical specialists. We begin by describing how to find associations and parent groups that can help you better understand and cope with your child’s condition. The chapter ends with a discussion on how to find a doctor that is right for your child.

Associations and Fragile X Syndrome In addition to associations or groups that your child’s doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your child’s insurance provider to find out if the cost will be covered):

Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 8

26 Fragile X Syndrome

·

Autism Research Institute Address: Autism Research Institute 4182 Adams Avenue, San Diego, CA 92116 Telephone: (619) 281-7165 Toll-free: (800) 688-8765 Fax: (619) 563-6840 Web Site: http://www.autism.com/ar Background: The Autism Research Institute (ARI) is an international voluntary organization dedicated to assisting parents and professionals concerned with autism. Autism is a nonprogressive neurologic disorder characterized by language and communication deficits, withdrawal from social contacts, and extreme reactions to changes in the immediate environment. ARI was founded in 1967 to conduct and foster scientific research designed to improve the methods of diagnosing, treating, and preventing autism. ARI also disseminates research findings to parents and other interested individuals. The Institute's databank contains approximately 29,000 detailed case histories of children with autism. The records were compiled from over 60 countries. In addition, the organization publishes a quarterly newsletter entitled 'Autism Research Review International.'. Relevant area(s) of interest: Fragile X Syndrome

·

Ehlers-Danlos National Foundation Address: Ehlers-Danlos National Foundation 6399 Willshire Boulevard, Suite 510, Los Angeles, CA 90048 Telephone: (323) 651-3038 Toll-free: (888) 663-4637 Fax: (323) 651-1366 Email: [email protected] Web Site: http://www.ednf.or Background: Ehlers-Danlos National Foundation is a voluntary self-help not-for- profit organization that is dedicated to providing emotional support and updated information to individuals affected by EhlersDanlos Syndrome (EDS) and their families. Ehlers-Danlos Syndrome is a group of inherited connective tissue disorders characterized by abnormalities of the skin, ligaments, and internal organs. Although symptoms and physical features may vary greatly depending upon the specific form of EDS present, many affected individuals may have thin, fragile, hyperextensible skin that may bruise easily; abnormally loose joints that are prone to dislocation; and widespread tissue fragility with bleeding and poor healing of wounds. Established in 1985, the

Seeking Guidance 27

Foundation serves as an informational link to the medical and research community on behalf of affected individuals. The Ehlers-Danlos National Foundation has worked to raise funds to support ongoing medical research and fund the Ehlers-Danlos Syndrome Database Manager, which was established to accumulate data on EDS. The Foundation produces educational and support materials including pamphlets, brochures, audiovisual aids, journal article reprints, and a newsletter entitled 'Loose Connections.' The Foundation also holds learning and research conferences. ·

Ehlers-Danlos Syndrome Support Group UK Address: Ehlers-Danlos Syndrome Support Group UK 1 Chandler Close, Richmond, North Yorkshire, DL10 5QQ, United Kingdom Telephone: 01748 823867 Toll-free: (800) 688-8765 Fax: 01748 823867 Email: [email protected] Web Site: http://ourworld.compuserve.com/homepages/EDS_UK/Ehlers.ht Background: The Ehlers-Danlos Syndrome Support Group UK is an international not-for-profit self-help organization dedicated to informing, encouraging, and assisting those with Ehlers-Danlos Syndrome (EDS) and their family members. Ehlers-Danlos Syndrome (EDS) is a group of rare inherited connective tissue disorders characterized by abnormalities of the skin, ligaments, and internal organs. Although symptoms and physical features may vary greatly depending upon the specific form of EDS present, many affected individuals may have thin, fragile, hyperextensible skin that may bruise easily; abnormally loose joints that are prone to repeated dislocations; widespread tissue fragility with bleeding and poor healing of wounds; and/or other abnormalities. Established in 1992, the Ehlers-Danlos Syndrome Support Group UK is committed to raising awareness of EDS among the medical and professional communities; supporting research into the causes, treatment, and cure of EDS; and enabling members of the organization to exchange information, support, and resources. The Group also maintains a listing of medical specialists who have experience with EDS; holds a biennial National Conference; produces booklets, information sheets, and other materials on all aspects of EDS; offers a 'Key Facts Medical Card' that is available in several languages to help affected individuals alert medical professionals to key aspects concerning EDS; and has a regular newsletter entitled 'Fragile Links.'.

28 Fragile X Syndrome

·

FRAXA Research Foundation Address: FRAXA Research Foundation 45 Pleasant Street, Newburyport, MA 01950 Telephone: (978) 462-1866 Toll-free: (888) 663-4637 Fax: (978) 463-9985 EWeb Site: http://www.fraxa.or Background: The FRAXA Research Foundation is a voluntary not-forprofit organization dedicated to providing support for individuals affected by Fragile X Syndrome, an X-linked disorder characterized by mental retardation, a large jaw, a high forehead, enlarged testes, and/or other abnormalities in affected males and, in some cases, mild mental retardation in females (heterozygotes). The Foundation is also committed to aiding the research efforts of concerned medical professionals throughout the United States. Founded in 1994 by parents of children with Fragile X Syndrome, the FRAXA Research Foundation is dedicated to educating public officials and the general population about Fragile X and to supporting ongoing medical research. The Foundation works toward these goals by awarding research grants to university-based scientists and physicians whose purpose is to find treatments for Fragile X Syndrome and by encouraging the publication of articles to increase awareness of Fragile X Syndrome. In addition, the FRAXA Research Foundation puts families with affected children in touch with one another and welcomes questions about this disorder from concerned individuals. The FRAXA Research Foundation produces educational and support materials including brochures, newsletters, and pamphlets. Individual chapters hold dances, golf tournaments, and other functions. Relevant area(s) of interest: Fragile X Syndrome

·

March of Dimes Birth Defects Foundation Address: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue, White Plains, NY 10605 Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email: [email protected] Web Site: http://www.modimes.or Background: The March of Dimes Birth Defects Foundation is a national not-for- profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. Through the Campaign for Healthier Babies,

Seeking Guidance 29

the March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it produces a wide variety of printed informational materials and videos. The March of Dimes public health educational materials provide information encouraging health- enhancing behaviors that lead to a healthy pregnancy and a healthy baby. Relevant area(s) of interest: Down Syndrome, Fragile X Syndrome, Klinefelter Syndrome, McCune Albright Syndrome, Phenylketonuria ·

National Fragile X Foundation Address: National Fragile X Foundation 1441 York Street, Suite 303, Denver, CO 80206 Telephone: (303) 333-6155 Toll-free: (800) 688-8765 Fax: (303) 333-6155 Email: [email protected] Web Site: http://www.nfxf.org Background: The National Fragile X Foundation is a nonprofit organization dedicated to promoting educational awareness and supporting research into the nature of Fragile X Syndrome. Fragile X Syndrome is an inherited defect of the X chromosome that causes mental retardation. Established in 1984, the National Fragile X Foundation produces a variety of educational and support materials. These materials include handbooks, brochures, a newsletter, pamphlets, and numerous audio-visual aids, such as 'Educational Strategies and Issues for Children with Fragile X Syndrome' and 'Fragile X Syndrome: Medical and Educational Approaches to Intervention.'. Relevant area(s) of interest: Fragile X Syndrome, FRAXA, Marker X Syndrome, X-Linked Mental Retardation and Macroorchidism

·

Ongwanada Fragile X Resource Centre Address: Ongwanada Fragile X Resource Centre 191 Portsmouth Avenue, Kingston, Ontario, K7L 1L2, Canada Telephone: (613) 548-4417 Toll-free: (800) 688-8765 Fax: (613) 548-174 Background: The Ongwanada Fragile X Resource Center is a voluntary organization that is dedicated to providing support and information concerning Fragile X Syndrome. Fragile X Syndrome is an inherited defect of the X chromosome that causes mental retardation. Established

30 Fragile X Syndrome

in 1948, the Center provides information on genetic counseling; genetic testing; parent and family support; networking options for parents; research opportunities; a registry; and educational materials. These materials include a newsletter, Spanish language materials, and pamphlets such as 'Fragile X Syndrome' or 'Alcohol and Pregnancy.' Fragile X Syndrome is also known as Martin-Bell Syndrome, FRAXA, Xlinked Mental Retardation and Macroorchidism, and Marker X Syndrome. Relevant area(s) of interest: Fragile X Syndrome, FRAXA, Marker X Syndrome, X-Linked Mental Retardation and Macroorchidism

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for parent associations. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about fragile X syndrome. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov. Simply type in “fragile X syndrome” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

Seeking Guidance 31

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “fragile X syndrome”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “fragile X syndrome” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with fragile X syndrome. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific medical conditions. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “fragile X syndrome” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms to discuss different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your child’s doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective. The following Internet sites may be of particular interest: ·

CCD http://hnb.dhs.vic.gov.au/.../bced7550634b825a4a25676c00482e1b/ 1d5baac3ccee72744a256744000645a3?OpenDocument

32 Fragile X Syndrome

·

Family Village http://www.familyvillage.wisc.edu/lib_frgx.htm

·

University of Kansas Medical Center Lay Advocacy Groups http://www.kumc.edu/gec/support

Finding Doctors All parents must go through the process of selecting a physician for their children with fragile X syndrome. While this process will vary, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:9 ·

If your child is in a managed care plan, check the plan's list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

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Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your child’s doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 9

Seeking Guidance 33

http://www.abms.org/newsearch.asp.10 You can also contact the ABMS by phone at 1-866-ASK-ABMS. ·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA's Web site: http://www.amaassn.org/aps/amahg.htm.

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare medical conditions. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Finding a Pediatrician The American Academy of Pediatrics (AAP) mission is “to attain optimal physical, mental, and social health and well-being for all infants, children, adolescents, and young adults.”11 The AAP maintains an online pediatrician referral service which is available to the public and free of charge. This service allows you to search the AAP’s database of its 55,000 members which include pediatricians, pediatric medical subspecialists, and pediatric surgical specialists practicing in the U.S., Canada, and internationally. To access the pediatrician referral service, log on to http://www.aap.org/referral/ and read the terms and conditions of use. Once you accept the terms, you can search for pediatricians by name, city, state, or country. All AAP members listed in the referral service database are boardcertified pediatricians.

Selecting Your Doctor12 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your child’s health insurance plan and 10 While board certification is a good measure of a doctor's knowledge, it is possible to receive quality care from doctors who are not board certified. 11 The American Academy of Pediatrics: http://www.aap.org/. 12 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

34 Fragile X Syndrome

if he or she is taking new patients. If the doctor is not covered by your child’s plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your first choice. During the first visit you will have the opportunity to evaluate your child’s doctor and to find out if your child feels comfortable with him or her.

Working with Your Child’s Doctor13 Research has shown that parents who have good relationships with their children’s doctors tend to be more satisfied with their children’s care. Here are some tips to help you and your child’s doctor become partners: ·

You know important things about your child’s symptoms and health history. Tell the doctor what you think he or she needs to know.

·

Always bring any medications your child is currently taking with you to the appointment, or you can bring a list of your child’s medications including dosage and frequency information. Talk about any allergies or reactions your child has had to medications.

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Tell your doctor about any natural or alternative medicines your child is taking.

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Bring other medical information, such as x-ray films, test results, and medical records.

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Ask questions. If you don't, the doctor will assume that you understood everything that was said.

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Write down your questions before the doctor’s visit. List the most important ones first to make sure that they are addressed.

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Ask the doctor to draw pictures if you think that this will help you and your child understand.

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Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Take information home. Ask for written instructions. Your child’s doctor may also have brochures and audio and videotapes on fragile X syndrome.

By following these steps, you will enhance the relationship you and your child have with the physician.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

13

Seeking Guidance 35

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help parents find healthcare professionals. These include:14 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

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Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Neurologic: Pertaining to neurology or to the nervous system. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Withdrawal: 1. a pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) a substancespecific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

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37

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on fragile X syndrome. All too often, parents who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on fragile X syndrome. In Part II, as in Part I, our objective is not to interpret the latest advances on fragile X syndrome or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with fragile X syndrome is suggested.

Studies 39

CHAPTER 3. STUDIES ON FRAGILE X SYNDROME Overview Every year, academic studies are published on fragile X syndrome or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on fragile X syndrome. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on fragile X syndrome and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and fragile X syndrome, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the

40 Fragile X Syndrome

format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “fragile X syndrome” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Dental Maturity Is Advanced in Fragile X Syndrome Source: American Journal of Medical Genetics. 83(4): 298-301. April 2, 1999. Contact: Available from John Wiley and Sons, Inc. Subscription Department, 9th Floor, 605 Third Avenue, New York, NY 10158. (212) 850-6645. Summary: Fragile X (FraX) syndrome is the most common cause of inherited mental retardation. The FraX gene (FMR1) has been cloned and the mutation causing the disease is now known. This article reports on a study in which the researchers estimated the effect of FraX on dental development in 28 affected boys (aged 4.9 to 17.6 years) and three carrier girls (aged 5.8, 10.4, and 12.7 years). Dental maturity, assessed on the basis of formation and of emergence, was compared with growth in stature and skeletal maturity. The mean relative dental age was advanced in FraX males, based on formation and on emergence. More pronounced advancement was seen in younger children. Dental maturity was advanced in heterozygous carrier girls as well. Height and skeletal maturity did not show a similar trend toward advanced development. Based on these findings, the authors conclude that advanced dental maturity is one of the clinical manifestations of the syndrome. 1 figure. 1 table. 28 references. (AA-M).

·

Epilepsy and EEG Findings in 18 Males With Fragile X Syndrome Source: Seizure. 10(1):60-63, January 2001. Summary: British researchers investigated the clinical features of epilepsy and the electroencephalographic (EEG) abnormalities found in a cohort of 24 males with fragile X syndrome from a screening program in Essex, 25 percent of whom had epilepsy. Researchers reviewed the EEG reports of 18 of the 24 participants, who ranged in age from 13 to 63 years, including all 6 participants with epilepsy. They had 32 EEG recordings from 18 males, and 9 males had more than one recording at different times. Overall, the EEG's showed a distinct improvement in only five of

Studies 41

the participants, while three people who had serial recordings (one with epilepsy) had no significant changes over time, and the EEG of one subject with epilepsy deteriorated over time. The most commonly detected abnormal EEG findings were rhythmic theta activity in 50 percent of the males and a slowing of background activity in 28 percent of the males. The daytime, drug-free sleep EEG's of four participants (two with epilepsy and two without) found abnormalities in two individuals (one with epilepsy and one without). The researchers conclude that the natural history of epilepsy in fragile X syndrome is more variable than previously thought. A significant proportion of participants continued to have seizures until a later age or developed late onset epilepsy, and partial epilepsy was as frequent as generalized seizures (contrary to previous findings). 2 tables, 27 references. ·

Fragile X Syndrome Source: ASHA. American Speech-Language-Hearing Association. 32(9): Insert. September 1990. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 897-0157. Website: www.asha.org. Price: $7.00 per 100. Summary: This article, provided in an insert in the ASHA journal, discusses Fragile X syndrome. Second only to Down syndrome as a genetic cause of mental retardation, Fragile X (fra X), or Martin-Bell syndrome results from an abnormal gene on the X sex chromosome which commonly causes moderate to severe mental retardation, delayed speech and language development, and subtle differences in physical features. Topics covered include behavior problems associated with fra X, incidence and prevalence statistics, diagnosing fra X, the genetic transmission of fra X, the learning abilities of individuals with fra X syndrome, delayed speech and language development in this population, and special education services and the role of an interdisciplinary approach. The insert concludes with information about a free booklet on fra X for families and educators. Designed to be photocopied and distributed to patients and their families, the insert provides information in clear, easy-to-understand language. It includes space for a clinician or facility to stamp a name and address.

42 Fragile X Syndrome

Federally-Funded Research on Fragile X Syndrome The U.S. Government supports a variety of research studies relating to fragile X syndrome and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.15 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to fragile X syndrome and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore fragile X syndrome and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for fragile X syndrome: ·

Project Title: A Program of Investigation into Fragile X Syndrome Principal Investigator & Institution: Warren, Stephen T.; William Patterson Timmie Professor Of; Biochemistry; Emory University 1380 S Oxford Rd Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 0-SEP-1997; Project End 0-JUN2006 Summary: (provided by applicant): Fragile X syndrome is a leading cause of mental retardation. The molecular basis of fragile X syndrome is the expansion of a trinucleotide repeat within the FMR1 gene, resulting in the absence of the encoded protein, FMRP. Although there has been a spectacular increase in the understanding of this disorder in recent years, much remains to be learned. To capitalize upon this trajectory of understanding, a well focused, multidisciplinary group effort to further elucidate the molecular basis of fragile X syndrome was initiated in September of 1997 with the funding of this program project composed of seven projects and one core. This revised proposal, in response to the

15 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies 43

formal review following three years of funded research, reflects a tighter, more thematic program of five interrelated and collaborative projects and one core at Emory University School of Medicine. These projects dramatically expand the scope of contemporary fragile X syndrome research and specifically address issues crucial for future investigation and intervention. A central program theme of FMRP expression and function cover the five broad, multidisciplinary projects. Project II will seek to understand the mechanistic details of chromatin changes leading to the transcriptional suppression of FMR1, the disease-causing consequence of full repeat expansion. Project I aims determine the biochemical and clinical consequences of smaller intermediate and premutation alleles that are found in 5% of the population. Projects V seeks to understand the biochemistry of FMRP with structure/function studies that are key in our continued understanding of the consequences of the absence of FMRP or a more subtle reduction of FMRP levels, studied in the prior two projects. Project III develops model systems where genetically modified mice and cell lines are produced where FMRP expression can be temporally and quantitatively controlled, both pre- and postnatally as well as in vitro. Along with the other projects, these novel biological resources will be used to explore new aspects of the pathophysiology of fragile X syndrome. This program of investigation into fragile X syndrome, by a highly interactive and multidisciplinary team with proven collaborative abilities, represents one of the largest research centers on this disorder in the world and aims to further our continued understanding of this important and common form of mental retardation. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Analyzing the Language Deficit in Fragile X Syndrome Principal Investigator & Institution: Simon, Jodie A.; Psychology; University of Denver Box 101562 Denver, Co 80208 Timing: Fiscal Year 2000; Project Start 1-JAN-2000 Summary: The proposed research is designed to investigate the underlying cognitive causes for the language deficit in fragile X syndrome( FXS) and its relation to the expression of the fragile X gene. Individuals with FXS have consistently been shown to have deficits in language, especially in the pragmatic and discourse aspects of social communication. Despite the devastating effects this is likely to have on social functioning, the nature of these deficits has yet to be determined. The proposed research will examine language performance of adults with FXS on three underlying mechanisms of language processing: set shifting, working memory, and semantic inhibition. These will be

44 Fragile X Syndrome

examined in a sample of high functioning adults with FXS, compared to a clinical comparison group of adults with autism matched on VIQ and chronological age, and a control group of normally-developing children matched on verbal mental age. Based on previous research, it is predicted that adults with FXS will demonstrate significant impairments in set shifting, working memory, but will show relatively intact semantic inhibition. Moreover, the proposed research will determine the extent to which performance on experimental language measures relates to a measure of the pragmatic aspects of conversational speech that have been central in clinical descriptions of speech in FXS, but that are not adequately documented by conventional language measures. Beyond addressing these hypotheses, this study constitutes a comprehensive evaluation of key components of discourse and pragmatic ability in FXS, and thus provide important insights into the nature of the language deficit. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Fragile X Syndrome: Banbury Conferences Principal Investigator & Institution: Greenough, William T.; Swanlund Professor of Psychology,; None; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 1-MAR-2001; Project End 8-FEB2006 Summary: (Investigator's abstract): The aim of this proposal is to hold a series of five annual interdisciplinary conferences on basic and clinical research relevant to fragile X syndrome (FXS). These meetings will be modeled on an initial conference held at the Banbury Conference Center, Cold Spring Harbor Laboratory, and Cold Spring Harbor, NY. The conferences are intended to bring together a broad range of scientists, both those working on FXS and others in allied, relevant fields. Another goal is to introduce young scientists to the area. Fragile X syndrome is the second leading genetic cause of mental retardation. It arises due to expansion of an unstable region of trinucleotide repeats it the 5' untranslated promoter region of the FMR-1 gene, causing hypermethylation of cytosine residues and silencing of the gene. A mouse FMR-l knockout model for the syndrome is available. The function of the fragile X mental retardation protein (FMRP) is not known, but it has recently been shown to be translated al synapses in response to activation of metabotropic receptors by the neurotransmitter glutamate. Relatively subtle phenotypic effects of the disorder are seen in the gross size of several brain regions and in the fine structure of synapses. As the first Banbury Conference indicated (summarized in Sec. C), advances in

Studies 45

our knowledge of this disorder are occurring very rapidly. There is no meeting devoted exclusively to basic and clinical research on FXS, and the participants found the first Banbury Conference extremely valuable. It is about proposed that future conferences be organized by a committee of leading researchers and clinicians, with the next meeting focused upon the neural basis of fragile X syndrome. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Gene Repression in Fragile X Syndrome Principal Investigator & Institution: Cedar, Howard; ; Hebrew University of Jerusalem Jerusalem 91904, Israel Jerusalem, Timing: Fiscal Year 2001; Project Start 1-MAY-2001; Project End 0-APR2006 Summary: (Adapted from the applicant?s description) Fragile X syndrome is caused by molecular defects in the structure and expression pattern of the FMR1 gene on the X chromosome. It is fairly well accepted that CGG repeat expansion leads to DNA methylation which then inhibits FMR1 activity, but very little is known about how this occurs. In order to decipher this mechanism, the investigators will use transgenic mice and embryonic cell culture systems. Studies on the cis acting elements and trans acting factors which regulate normal DNA methylation in the early embryo will form the basis for investigating the aberrant factors which bring about faulty methylation at the FMR1 locus. Studies on chromatin structure will be aimed at explaining how DNA methylation actually causes transcriptional inhibition. Another structural parameter which is affected in fragile X syndrome is DNA replication timing. Using FISH technology, the investigators plan to elucidate the mechanism which causes the FMR1 region to replicate so late in the cell cycle, and thus understand how this brings about regional repression. Unlike other genetic diseases, the molecular changes in fragile X syndrome are epigenetic in nature, so that once these mechanisms have been better defined, it should be possible to design new strategies for reactivating FMR1, thereby reversing the molecular defect. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

·

Project Title: Molecular Genetics and Epigenetics of Fragile X Syndrome Principal Investigator & Institution: Laird, Charles D.; Professor of Zoology; Zoology; University of Washington 3935 University Way Ne Seattle, Wa 98195

46 Fragile X Syndrome

Timing: Fiscal Year 2000; Project Start 1-APR-1995; Project End 1-AUG2003 Summary: (Adapted from investigator's abstract) This project investigates several aspects of DNA methylation and replication related to fragile X syndrome. The applicant and colleagues have observed that with repeat expansion the FMR1 gene is abnormally methylated (and thereby transcriptionally inactivated) and that its replication is abnormally delayed. The methylation pattern, as determined by protection from bisulfite conversion, showed a remarkable dichotomy: alleles are either highly methylated or not, with few intermediates. The degree of methylation varies, however, with some sites (apparently binding sites for transcription factors) less methylated than others. The methylation pattern is relatively conserved through cell division. DNA replication, as determined by BrdU incorporation in cells by sorted by DNA content and cyclin B1 staining, occurs quite late in the cell cycle, within 90 minutes of mitosis for FMR1 and as much as 1% of total genomic DNA. This observation cells into question the traditional concept of a gap (G2) between DNA replication and chromosome condensation for mitosis, and it may explain sites of chromosome fragility. In the renewal period, the applicants will further pursue the phenomena of DNA methylation and delayed replication. They will characterize the methylation pattern of the FMR1 region in different cell types at different stages of the cell cycle. They will examine clonal conservation of methylation patterns through cell division. They will study late DNA replication in cells sorted with an antibody to phosphorylated histone H3 and in conditions that promote chromosome fragility. Finally they will further develop and use a technique called "boomerang PCR" to determine the direction of DNA synthesis in relation to methylation. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Transcription and RNA Binding in Fragile X Syndrome Principal Investigator & Institution: Reines, Daniel; ; Emory University 1380 S Oxford Rd Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 0-SEP-1997; Project End 0-JUN2006 Summary: Fragile X syndrome is the most common form of inherited mental retardation. It results from loss of function of the FMR1 gene product. Virtually all cases are due to the specific transcriptional silencing of FMR1 -- hence, the syndrome can be considered a transcriptional disease. Silencing is an indirect consequence of the expansion to more than 200 copies, of a CGG repeat (normal modal size

Studies 47

of 30) in FMR1's 5'-untranslated region. Expansion results in the aberrant de novo methylation of cytosines both in CG dinucleotides within the repeat, and in the neighboring upstream CpG islands in the FMR1 promoter. Hypermethylation is thought to be a proximal cause of the transcriptional inactivity of FMR1 in patients. However the molecular mechanism by which methylation leads to loss of transcription of FMR1 is unknown. Patient FMR1 is packaged in hypoacetylated histones H3 and H4, another characteristic of transcriptionally silent loci. Drugs that reverse the methylation state of FMR1 DNA result in a relative hyperacetylation of histones H3 and H4 at FMR1 and restore transcription. A current model of methylation-mediated gene repression suggests that recruitment of histone deacetylases to the promoter via methyl cytosine binding proteins establish a closed chromatin environment at mutant FMR1. The long range objective of this project is to understand the molecular mechanism of transcriptional silencing of patient FMR1, and to ultimately reverse it. Aim 1 will characterize transcription factors, including histone acetyltransferase activities, that drive normal FMR1 promoter function. Aim 2 will identify repression complexes that bind methylated DNA and deacetylate histones in mutant, expanded FMR1 alleles. Aim 3 will test the idea that histone acetylation is important for FMR1 transcription by exogenously expressing histone acetyltransferase and directing it to the mutant, methylated FMR1 promoter. Promoter occupancy will be evaluated in patient cells with intermediate states of remodeled chromatin. Results obtained from this experimental system will allow identification of the steps involved in transcription of a clinically important gene residing in its natural chromosomal context. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Attention, Memory, and Executive Function in Fragile X Principal Investigator & Institution: Bailey, Donald B.; Director of Early Childhood Research; F.P. Graham Child Devel Ctr; University of North Carolina Chapel Hill Chapel Hill, Nc 27514 Timing: Fiscal Year 2001; Project Start 1-JUL-2001; Project End 0-JUN2006 Summary: Although considerable research has examined general intellectual functioning and adaptive behavior in fragile X syndrome (FXS), only a few studies have examined specific domains of neurocognitive functioning, especially in males. Existing research has been limited by cross-sectional designs, lack of comparison groups, a wide age range in the samples, and inconsistencies in assessment methodologies. The proposed project would add substantially to our

48 Fragile X Syndrome

knowledge about neurocognitive function in FXS by conducting more detailed, systematic, and expansive assessments of attention, memory, and executive function. The project builds on an existing sample of children with FXS participating in a prospective, longitudinal study who are about to enter puberty. We will describe in detail the nature of cognitive function and development over time during early adolescence, and relate function and development to other clinical, genetic, neuropsychological, biological, and sociodemographic variables in order to describe more precisely the FXS phenotype and understand the variability within this population. The study will incorporate a sample of 68 children with FXS between the ages of 8 and 13 years. A comparison group of 68 mental-age-matched typically developing children will provide insights into relative cognitive strengths and weaknesses in FXS in relation to their own mental age. Each child will be assessed annually using a comprehensive battery of attention, memory, and executive function measures. Additional measures will be collected of FMRP, pubertal status, socioeconomics status, temperament, autistic behavior, language development, visual processing skills, and behavior problems. These additional assessments will test the relationship between protein expression and neurocognitive function, identify changes in patterns of development as a function of puberty, provide some insights into the role of environment in affecting outcomes, and increase the specificity of the FXS phenotype by providing a comprehensive description of a range of features likely to be associated with FXS. A range of analytic procedures, including hierarchical linear modeling, will be used to answer four specific aims related to determining neurocognitive profiles, comparing profiles with the comparison group, examining change over time, and testing the relationship between neurocognitive function and other variables of interest. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Expression and Function of FMRP During Development Principal Investigator & Institution: Irwin, Scott A.; None; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2000; Project Start 1-FEB-2000 Summary: Our laboratory has recently obtained evidence from an in vitro synaptoneurosome preparation that the fragile X gene product, a protein termed FMRP, is translated from mRNA at locations near synapses in response to glutamatergic activation of metabotropic receptors. This finding complements other work on the fragile X gene (FMR-1) and the fragile X syndrome, a form of mental retardation correlated with the

Studies 49

absence of normal FMRP expression, all of which suggest that FMRP may play a role in the process whereby synaptic activity during development and/or learning results in a structural and functional maturation of the synapse. We propose a series of basic studies of the rodent brain designed to further explore in vivo, 1) the spatio-temporal pattern of the expression of FMRP during development, 2) the possible correlation of FMRP expression with other major developmental processes, such as synaptogenesis, in order to explore possible reasons for the pathological effects of FMRP deficiencies on brain development, and 3) the effects of behavioral experience on FMRP expression in brain regions known to exhibit structural plasticity in response to behavioral experience manipulations, studying visual cortex in monocularly deprived animals and animals exposed to an enriched environment, and motor cortex in animals after acrobatic motor skill learning. Fragile X syndrome, which can arise from a mutation that prevents gene expression or from point mutations affecting the structure of the gene product, is one of the most common forms of inherited mental retardation known. Furthermore, it is commonly associated with autism and attention deficit hyperactivity disorder. Knowledge of the role of FMRP in synapse maturation and brain function may well give rise to treatments for these syndromes. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Expression of the Fragile X Gene Principal Investigator & Institution: Hagerman, Paul J.; Professor; Biological Chemistry; University of California Davis Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 1-APR-2002; Project End 1-MAR2007 Summary: (provided by applicant): Fragile X syndrome (FXS), a trinucleotide (CGG) repeat expansion disorder, is the leading heritable form of mental retardation, and is associated with a variety of learning disorders and behavioral problems in childhood. FXS is generally believed to arise when the CGG element of the fragile X mental retardation 1 (FMR1) gene expands beyond -200 repeats (full mutation), and the upstream promoter region and CGG repeat become methylated, the latter event leading to transcriptional silencing and the consequent failure to produce FMRI protein (FMRP). However, for males with premutation alleles (55-200 repeats) FMRI mRNA levels in peripheral blood leucocytes are significantly elevated, by as much as ten-fold for males with premutation alleles that exceed 100 repeats, and for males with full mutation alleles that remain unmethylated. These observations suggest that the FMR1 gene may be up-regulated. Identification of the reasons for the elevated mRNA levels is the first major objective of the

50 Fragile X Syndrome

proposed research. It has also been demonstrated that leucocytes from the majority of males with FMRI alleles that are fully expanded and (apparently) fully methylated continue to produce significant levels of FMR1 mRNA. This surprising result, which is not due to transcription from premutation alleles or a small fraction of fullyunmethylated alleles, suggests that the interplay between methylation and silencing is less direct than had been supposed. Identification of the means by which hypermethylated FMR1 genes sometimes escape silencing is the second major objective of the proposed research. These two basic observations have important ramifications for understanding and eventually treating FXS. Elucidation of the signals that regulate transcriptional activity (both for up-regulation and for silencing) will hopefully lead to molecular therapies that can modulate the expression of the endogenous FMR1 gene. Methods of approach will continue to be quantitative (fluorescence) RT-PCR, and will incorporate chromatin immunoprecipitation as an assay for acetylation status of FMR1-associated histones. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: FMRP and MRNA Translation Principal Investigator & Institution: Feng, Yue; ; Emory University 1380 S Oxford Rd Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 0-SEP-1997; Project End 0-JUN2006 Summary: Fragile X syndrome is caused by the lack of the functional protein product encoded by the FMR1 gene, designated as FMRP. Although the exact function of FMRP remains to be defined, accumulating evidence supports the concept that FMRP is a messengerribonucleoprotein (mRNP), which selectively associates with translating polyribosomes via poly-A RNA in living cells. The functional importance of FMRP-polyribosome association and mRNP complex formation has been indicated by the fact that the 1304N point mutation, identified from an unusually severe fragile X patient, causes incorporation of FMRP into abnormal mRNP particles that fail to associate with polyribosomes. These observations have led the applicant to hypothesize that FMRP interacts with its mRNA targets within the mRNP complexes and controls the translation activity of these mRNAs. This hypothesis is reinforced by the applicant?s recent finding that FMRP inhibits translation in vitro in a dose-dependent and mRNA-selective manner. This proposal aims to further test the above hypothesis using in vitro translation systems, cultured cell lines, as well as wild type and fmrl knockout neurons by the following three specific aims: 1). To test the hypothesis that the selectivity of FMRP as a translation suppresser in the rabbit reticulocyte lysate

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(RRL) is determined by the FMRP-binding activity of the translation templates; 2). To elucidate possible mechanisms for the in vitro translation inhibition caused by FMRP; 3). To test the hypothesis that FMRP inhibits translation in living cells, and extracellular signals modulates FMRP?s influence on translation. The proposed research will address how FMRP may influence translation, and whether FMRP?s influence on translation can be regulated to accommodate cell function. Answers to these questions should greatly improve our knowledge on FMRP?s function, which not only facilitates the elucidation of the pathogenesis of fragile X syndrome, but more importantly helps to understand how RNA-protein interactions may regulate translation to impact brain function and development. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Fragile X Related Genes in Mental Retardation Principal Investigator & Institution: Nelson, David L.; Molecular and Human Genetics; Baylor College of Medicine 1200 Moursund Ave Houston, Tx 77030 Timing: Fiscal Year 2000; Project Start 0-AUG-1999; Project End 1-JUL2004 Summary: Fragile X syndrome (MIM number 30955) is among the most common human single gene disorders, and is the leading cause of inherited mental retardation, with an estimated frequency of 1/20001/4000 individuals world-wide. The gene defective in fragile X syndrome (FMR1) was identified by positional cloning in 1991, yet its function, and the consequences of its absence remain unknown. The FMR1 protein interacts with mRNAs in a variety of cell types, and has been shown to associate with ribosomes. These apparently fundamental properties are difficult to reconcile with the relatively mild phenotype found in fragile X patients and in a mouse knockout of the Fmr1 gene. The central hypothesis of the project proposed here is that two FMR1-related proteins, FXR1 and FXR2 provide redundancy of function for FMR1. This redundancy masks the phenotypic consequences of loss of function mutations in humans and mice that would allow better definition of the function of FMR1. In order to test this hypothesis, mutations in the Fxr1 and Fxr2 genes are proposed. These will be introduced into the mouse genome with the capability to provide conditional knockouts using the site specific recombinase Cre derived from phage P1, which recognizes lox P sites for recombination. Mutant mice will be analyzed by biochemical, histological and behavioral methods in order to determine the consequences of the absence of one or more of these genes. Conditional mutations will be created to investigate tissue specific or

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developmental timing effects of gene ablation. Mutations in the Fxr1 and Fxr2 proteins, especially in combination with Fmr1 mutations, should provide resolution of the redundancy question. Such mutations and combinations of mutations will also provide important evidence for the functions of these genes. Results from this project will provide additional data regarding the normal function of FMR1 and the consequences of its absence in fragile X syndrome. These data will allow further investigation of potential therapeutic intervention in this common form of mental retardation. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Genotype-Phenotype Relationships in Fragile X Families Principal Investigator & Institution: Hagerman, Randi J.; Professor; Pediatrics; University of California Davis Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 5-JUN-1998; Project End 0-MAY2006 Summary: (provided by applicant): Our studies over the last 2 and a half years have lead to significant breakthroughs in. our understanding of genotype-phenotype relationships in fragile X syndrome. We have discovered a significant translation problem in the conversion of mRNA into FMR1 protein (FMRP), which begins in the premutation range. Significant elevation in. mRNA levels abo"e controls are seen in males and females with the premutation. For premutation carriers who are significantly affected, mRNA levels may be up to 10 times normal and associated with a mild FMRP deficit. Executive function deficits are usually present in males with the premutation and a subgroup of these males who are older than 50 years demonstrate a cerebellar tremor associated with brain atrophy and a slowly progressive neurocognitive decline. These problems may be related to additive genetic effects and/or elevated mRNA levels. We do not yet know the prevalence of these neurological problems in older males with the premutation, or whether these problems may also occur in older females with the premutation. We also have preliminary evidence that autism in association with fragile X syndrome may be related to background gene effects. Our competitive renewal will focus on both of these problems: the association of autism and fragile X syndrome, and the emerging neurological phenotype in. older carriers with the premutation. We will study these problems within the format of our family study design (40 families per year) which provides controls within the family and allows an analysis of background gene effects with the pedigree analysis statistical approach from our collaborators Drs. Danuta Loesch and Richard Huggins at La Trobe University in Melbourne, Australia. We will utilize state of the art autism

Studies 53

diagnostic tools including the Autism Diagnostic Interview (ADI-R) and the Autism Diagnostic Observation scale (ADOS-G) in addition to a family questionnaire to assess the extended autism phenotype. We will expand the family studies to consistently include grandparents and their siblings to better understand the aging process in carriers with neurological and neuropsychological assessments. Volumetric MRI studies will be done on older carriers with and without tremors and controls and all phenotypic findings will be correlated with FMR1 gene studies including mRNA, FMR1 protein, COG repeat number, methylation status, and activation ratio. In addition to the FMR1 gene studies, we will assess additional alleles, in collaboration with Gerard Schellenberg, Ph.D., including the serotonin receptor (5-HTT), and the GABA receptor (GABRB3) which are associated with autism, and ApoE and tau haplotypes associated with neurodegeneration. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Linguistic Communication and Mental Retardation Principal Investigator & Institution: Abbeduto, Leonard J.; Professor; Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 500 Lincoln Dr Madison, Wi 53706 Timing: Fiscal Year 2000; Project Start 1-SEP-1987; Project End 0-JUN2003 Summary: This project will investigate the development of discourse in adolescents who have mental retardation due to Down syndrome (DS) or fragile X syndrome (FXS). Each syndrome is characterized by impairments in the domains of behavioral functioning that support discourse development (e.g., cognition, receptive language) and, thus, individuals with either syndrome are likely to find discourse to be especially challenging. There are also differences in the behavioral phenotypes of DS and FXS, which may lead to different profiles of discourse problems. There are few data on the discourse skills of individuals with DS or FXS and fewer data still on discourse problems that may be specific to one syndrome or the other. The need for such data is especially acute during the adolescent years. During adolescence, preparation begins for adult roles that demand expertise in discourse. This project will examine discourse in adolescents with DS and adolescents with FXS from a model in which discourse is seen to emerge from the collorative activity of people working toward a common goal. This project has three specific aims. This first is to determine (a) whether discourse development is more severely disrupted in these adolescents than expected from their levels of functioning in domains that support discourse development (i.e., cognition, linguistic ability) and (b) whether

54 Fragile X Syndrome

it is disrupted differently in the two syndromes. The second aim is to (a) identify the ways in which developments of nonverbal cognition, language, social cognition, speech, and hearing contribute to the ability of these adolescents to collaborate effectively and (b) determine whether these domains make different contributions to discourse for DS and FXS. The third aim is to determine what syndrome-specific impairments (i.e. psychopathology and auditory memory problems) contribute to discourse collaboration. Five studies will address these aims. In each, participants will engage in a referential task that is designed to highlight differences between the syndromes. Comparisons with younger, typically developing children will determine the extent to which discourse development is disrupted in each syndrome. Measures will be taken of domains in which there are syndrome-shared impairments. Hierarchial multiple regression will be used to examine the contributions of these domains to the discourse collaboration of the DS and FXS groups. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neurological Function of Fragile X Gene in Drosophila Principal Investigator & Institution: Broadie, Kendal S.; Biology; University of Utah 110 Park Bldg Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 0-APR-2001; Project End 1-MAR2006 Summary: (Adapted from the applicant's Description) Fragile X syndrome is caused by a triplet nucleotide CGG expansion within the 5' untranslated region in the gene FMR1, resulting in the absence of the gene product, FMRP, a selective RNA-binding protein associated with ribosomes and enriched in nervous system. The compelling challenge in fragile X research is to understand the cellular pathogenesis by which the lack of FMRP gives rise to mental retardation and associated behavioral abnormalities. One potential approach is to assay the FMR1 within a simpler, well-characterized model organism. The investigators propose to uncover the synaptic defects of fragile X syndrome, and identify and characterize novel FMR1 interacting genes in Drosophila. They have identified a FMR1 gene homologue in Drosophila, dFXR, and hypothesized that the function of FMR1 is conserved between Drosophila and human. Taking advantage of powerful Drosophila genetics, they propose to systemically investigate the neurological functions of FMRP by a three-step approach. Specific Aim 1 will generate a series of dFXR mutants, including "loss of function" mutants by targeted knockout and "gain of function" mutants by manipulating the expression of transgenes. Specific Aim 2 will characterize the neurological functions of dFXR,

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focusing on synaptic development, function, and plasticity. Specific Aim 3 will search for novel dFXR interacting genes with a genetic enhancer / suppressor screening and microarray technology. This application therefore complements and extends the parallel studies on mammalian systems. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neurophysiological-Molecular Association in FXS Infants Principal Investigator & Institution: Hill Karrer, Jennifer; R L Smith Mental Retard Center; University of Kansas Medical Center Medical Center Kansas City, Ks 66103 Timing: Fiscal Year 2000; Project Start 1-JUL-2000; Project End 0-JUN2005 Summary: Fragile X syndrome (FXS) is an inherited abnormality responsible for mild to moderate mental retardation among individuals with expanded DNA material (greater than 230 CGG repeats) on the FMR-1 gene. Prevalence in the general population is problematic since one in 250 females are carriers of FXS. The purpose of this research project is to investigate the impact of FXS on early neurocognitive development among infants, toddlers and preschoolers. Neurophysiological, molecular and behavioral measures will be integrated in this study to explain, in part, biobehavioral dysfunction responsible for the decline in cognitive functioning during the first five years of life. For the first time, event-related brain potentials (ERPs) will be recorded from infants and children with FXS. Unaffected and premutation siblings of subjects with FXS and (unrelated) subjects without known risk of developmental delay will serve as comparison groups. Subjects with Down syndrome (DS) will likewise serve as a contrast study group. Studies within this project will investigate syndrome-specific strengths and weaknesses related to attention, expectancy, stimulus encoding, sequential information processing, visual recognition memory and social gaze. Results will therefore provide new knowledge concerning genotypic-specific neural organization of early cognitive development among subjects with FXS (as compared to subjects with DS). Specific ERP components will thereafter be correlated to CGG repeat region size, FMRP (FMR-1 gene protein), percent methylation, mRNA and, among females, the X activation ratio. The integration of neurophysiological, molecular and behavioral measures through Hierarchical Linear Modeling will assess the impact of FXS upon human neurocognitive development. At the conclusion of our projects, measures developed within our studies will provide new methodologies in the assessment of the effectiveness of early intervention. Outcome measures

56 Fragile X Syndrome

will likewise provide the means to critique subsequent pharmacotherapy and gene therapy specific to FXS. Results of this study will provide a time course of onset of neuropathology due to deficiencies of FMRP during early development and, accordingly, provide a more precise target of the ideal age at which FMRP protein replacement should be applied among children with FXS. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

E-Journals: PubMed Central16 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).17 Access to this growing archive of e-journals is free and unrestricted.18 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “fragile X syndrome” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for fragile X syndrome in the PubMed Central database: ·

A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication by R. Scott Hansen, Theresa K. Canfield, Alan D. Fjeld, Steven Mumm, Charles D. Laird, and Stanley M. Gartler; 1997 April 29 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20767

·

The Fragile X Syndrome d(CGG)n Nucleotide Repeats Form a Stable Tetrahelical Structure by M Fry and LA Loeb; 1994 May 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43907

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 17 With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 18 The value of PubMed Central, in addition to its role as an archive, lies the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 16

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to the public.19 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with fragile X syndrome, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “fragile X syndrome” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “fragile X syndrome” (hyperlinks lead to article summaries): ·

Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome. Author(s): Nielsen DM, Derber WJ, McClellan DA, Crnic LS. Source: Brain Research. 2002 February 8; 927(1): 8-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11814427&dopt=Abstract

·

Fragile X syndrome. Author(s): Gelbart M. Source: Nurs Times. 1998 November 25-December 1; 94(47): 45. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9934149&dopt=Abstract

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

19

58 Fragile X Syndrome

Vocabulary Builder Aberrant: Wandering or deviating from the usual or normal course. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Auditory: Pertaining to the sense of hearing. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Cerebellar: Pertaining to the cerebellum. [EU] Chromosomal: Pertaining to chromosomes. [EU] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. [NIH] Endogenous: Developing or originating within the organisms or arising from causes within the organism. [EU] Extracellular: Outside a cell or cells. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or

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absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Particle: A tiny mass of material. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a

60 Fragile X Syndrome

specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Skeletal: Pertaining to the skeleton. [EU] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH] Tremor: An involuntary trembling or quivering. [EU]

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CHAPTER 4. PATENTS ON FRAGILE X SYNDROME Overview You can learn about innovations relating to fragile X syndrome by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.20 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.

20Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Patents on Fragile X Syndrome By performing a patent search focusing on fragile X syndrome, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on fragile X syndrome: ·

Diagnosis of the fragile X syndrome Inventor(s): Caskey; C. Thomas (Houston, TX), Nelson; David L. (Houston, TX), Pieretti; Maura (Houston, TX), Warren; Stephen T. (Clarkston, GA), Oostra; Ben A. (Rotterdam, NL), Fu; Ying-hui (Houston, TX) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 6,180,337 Date filed: August 29, 1991 Abstract: A sequence of the FMR-1 gene is disclosed. This sequence and related probes, cosmids and unique repeats are used to detect X-linked diseases and especially the fragile X syndrome. Also, methods using methylation-sensitive restriction endonuclease and PCR primer probes were used to detect X-linked disease. Excerpt(s): This invention relates to the field of molecular diagnosis of the fragile X syndrome. ... The fragile X syndrome is the most frequently encountered form of inherited mental retardation in humans and has a prevalence estimated to be 1/1250 males. The fragile X syndrome segregates as an X-linked dominant disorder with reduced penetrance. Either sex when carrying the fragile X mutation may exhibit mental deficiency. It has been shown that approximately 30% of carrier females are penetrant and that 20% of males carrying the fragile X chromosome are normal but may transmit the disorder and have fully penetrant grandsons. In addition to the mental retardation which is variable in severity, penetrant males exhibit additional phenotypic involvement including macroorchidism and distinctive facies. Since fully penetrant males rarely reproduce, it has been suggested that the frequency of new mutations of the fragile X site may be as high as 1/3000 germ cells to

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maintain the population frequency. ... The fragile X syndrome, as implied by its name, is associated with a fragile site expressed as an isochromatid gap in the metaphase chromosome at map position Xq 27.3. The fragile X site is induced by cell culture conditions which perturb deoxypyrimidine pools and is rarely observed in greater than 50% of the metaphase spreads. Neither the molecular nature of the fragile X site, nor its relationship to the gene responsible for the clinical expression of the syndrome is understood. However, based upon genetic linkage studies, as well as in situ hybridizations, the fragile X site and its associated gene are tightly linked if not coincident. Web site: http://www.delphion.com/details?pn=US06180337__ ·

Methods and compositions for the diagnosis of fragile X syndrome Inventor(s): Das; Soma (Chicago, IL), Ledbetter; David H. (Chicago, IL) Assignee(s): Arch Development Corporation (Chicago, IL) Patent Number: 6,143,504 Date filed: October 27, 1999 Abstract: The present invention relates generally to the field of diagnostics. More particularly, it concerns the use of methylation-specific PCR in order to identify those males having Fragile X syndrome. The present invention provides a method in which amplification specific for the methylated FMR1 sequence is observed in all individuals with a full mutation, while all normal and premutation individuals show only amplification specific for the unmethylated sequence, thus allowing affected and unaffected males to be distinguished. A full mutation in the presence of mosaicism also may detectable by this method. Thus, methylation-specific PCR is demonstrated as a rapid and reliable tool for the diagnosis of fragile X. Excerpt(s): The present invention relates generally to the fields of diagnostics. More particularly, it concerns the use of methylation-specific PCR in order to identify those individuals having Fragile X syndrome. ... The fragile X syndrome is the most common inherited form of mental retardation and developmental disability. This condition afflicts approximately 1 in 2500 males and 1 in 5000 females. Males with fragile X syndrome usually have mental retardation and often exhibit characteristic physical features and behavior (Hagerman and Silverman, 1992; Warren and Nelson, 1994). Perhaps the most debilitating clinical feature noted in individuals with Fragile X is that of behavior, these characteristics include behavior similar to autism and attention deficit disorder, obsessive-compulsive tendencies, hyperactivity, slow

64 Fragile X Syndrome

development of motor skills and anxiety fear disorder. When these disabilities are severe and occur simultaneously, the condition is sometimes described as autism, and may be associated with any degree of intelligence. Minorities of individuals with fragile X have autism. Many more have some of the above features. Particularly common in fragile X (and much less so in other conditions) is the combination of a likable, happy, friendly personality with a limited number of autistic-like features such as hand-flapping, finding direct eye contact unpleasant, and some speech and language problems. ... Fragile X is an X chromosome-linked condition that is characterized by a visible constriction near the end of the X chromosome, at locus q27.3, and there is a tendency for the tip of the X-chromosome to break off under certain conditions in tissue culture. The pattern of inheritance of this condition is atypical of that associated with X-linked conditions. In typical X-linked genetic defects, there is a 50% probability that the male offspring of a female carrier will be afflicted by the defect. Additionally, all males who carry the abnormal gene are afflicted by the X-linked disorder in the typical pattern. Furthermore, since females have two X chromosomes, they normally do not suffer the effects of a single damaged X chromosome. In fragile X syndrome, however, carrier males are phenotypically normal. Certain individuals are carriers of fragile X in that they have a premutation in the FMR1 gene but do not show symptoms of fragile X. Carrier men (transmitting males) pass the premutation to all their daughters but none of their sons. Each child of a carrier woman has a 50% chance of inheriting the gene. The fragile X premutation can be passed silently down through generations in a family before a child is affected by the syndrome. Moreover, about one-third of the females inheriting the fragile X chromosome are afflicted with the disease. Daughters of carrier males are generally non-expressing carriers, but may have afflicted sons. Afflicted daughters occur more frequently among the offspring of carrier mothers than among the offspring of carrier fathers (Brown, 1990). Web site: http://www.delphion.com/details?pn=US06143504__

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Patent Applications on Fragile X Syndrome As of December 2000, U.S. patent applications are open to public viewing.21 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years).

Keeping Current In order to stay informed about patents and patent applications dealing with fragile X syndrome, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “fragile X syndrome” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on fragile X syndrome. You can also use this procedure to view pending patent applications concerning fragile X syndrome. Simply go back to http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH]

21

This has been a common practice outside the United States prior to December 2000.

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CHAPTER 5. BOOKS ON FRAGILE X SYNDROME Overview This chapter provides bibliographic book references relating to fragile X syndrome. You have many options to locate books on fragile X syndrome. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some parents, however, prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on fragile X syndrome include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is available for loan.

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Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go to http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “fragile X syndrome” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on fragile X syndrome: ·

Genetic Disorders and Birth Defects: A Compendium of AAP Guidelines and Resources for the Primary Care Practitioner Source: Elk Grove Village, IL: American Academy of Pediatrics (AAP). 1997. 130 p. Contact: Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 4339016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. Price: $24.95 each (members); $29.95 each (nonmembers); plus shipping and handling. Order Number B-MA0097. Summary: This volume provides a compendium of the American Academy of Pediatrics (AAP) guidelines and resources for health care providers who are working with patients who have genetic disorders and birth defects. The compendium serves as a diagnostic and management resource guide for pediatricians and primary care physicians. Although some of the disorders covered are relatively uncommon, it is likely that most pediatricians will encounter and care for a few such patients in their practice panel. The authors emphasize that early intervention services, multidisciplinary care, and developmental assessment and management form a major part of continuing care for many children with genetic conditions. The AAP Policy Statements are provided on folic acid for the prevention of neural tube defects, issues in newborn screening, maternal phenylketonuria, maternal serum alpha-fetoprotein screening, newborn screening for congenital hypothyroidism, newborn screening fact sheets, and prenatal genetic diagnosis for pediatricians. In addition, policy statements are provided for the health supervision of children born with the following conditions: achondroplasia, Down syndrome, fragile X syndrome, Marfan syndrome, neurofibromatosis, sickle cell disease, and Turner syndrome. Each Policy Statement includes references. The

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compendium includes extensive appendices, covering topics including fetal alcohol syndrome, general principles of care for children and adolescents with genetic and other chronic health conditions, hospital stays, medical homes, preventive pediatric health care, and transition of care provided for adolescents with special health care needs. The compendium also lists the references where the policy statements were first published, the contact information for national and regional genetic organizations, and the members of the AAP Section on Genetics and Birth Defects. ·

Children with Disabilities. 4th ed Source: Baltimore, MD: Paul H. Brookes Publishing Company. 1997. 940 p.

Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: www.brookespublishing.com. Price: $49.95 plus shipping and handling. ISBN: 1557662932. Summary: This textbook addresses the impact of disabilities on child development and function. Thirty-six chapters, each written by subject specialists, cover chromosomes and genetics; heredity; birth defects, prenatal diagnosis, and fetal therapy; growth before birth; the birth process; the first weeks of life; prematurity and low birth weight infants; substance abuse and the infants of drug-dependent mothers; HIV and AIDS, including transmission from mother to child; nutrition; vision; hearing; language; the brain and nervous system; muscles, bones, and nerves; mental retardation; Down syndrome; fragile X syndrome; PKU and other inborn errors of metabolism; mental retardation and psychiatric disorders; autism and other pervasive developmental disorders; attention deficit or hyperactivity disorder; learning disabilities; cerebral palsy; neural tube defects; seizure disorders; traumatic brain injury (TBI); the feeding process and feeding problems in children with disabilities; dental care; behavior management and promoting adaptive behavior; technological assistance, notably innovations that promote independence; rehabilitation interventions, including physical therapy and occupational therapy; ethical choices; caring and coping and the family of a child with disabilities; adulthood and transition issues; and the changing health care environment. Each chapter begins with a list of learning objectives. Most chapters include one or more stories, or case studies, to illustrate the conditions and issues discussed in the chapter. As medical terms are introduced in the text, they appear in bold type; definitions for these terms are provided in a glossary. More than 200 drawings, photographs, x-rays, and tables reinforce the points of the text.

70 Fragile X Syndrome

Each chapter closes with a final section that reviews its key elements and abstracts the material covered. A reference list is included with each chapter. There are four appendices to the book: a glossary; a list of syndromes and inborn errors of metabolism (more than 150 inherited disorders causing disabilities); indications and side effects of medications often prescribed for children with disabilities; and a directory of national organizations, specialized hospitals, protection and advocacy programs, and university affiliated programs that can provide assistance to families and professionals. An extensive subject index concludes the volume. ·

A-Z Reference Book of Syndromes and Inherited Disorders Source: London, England: Chapman and Hall. 1996. 394 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 2386777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. Price: $42.95 plus shipping and handling. ISBN: 0412641208. Summary: This book provides a practical reference for both caregivers and those with a syndrome or inherited disorder. The author describes the disorders and problems of both children and adults, and considers the day-to-day management of conditions. The book is written in nontechnical language while still providing enough detail for medical, nursing, and midwifery professionals. The syndromes and disorders are listed alphabetically by name. Those specifically related to deafness, communication, and speech and language include achondroplasia, Alport's syndrome, Apert's syndrome, Asperger's syndrome, Batten's disease, Beckwith-Wiedeman syndrome, CHARGE syndrome, Cockayne syndrome, Cornelia de Lange syndrome, Crouzon's syndrome, Down's syndrome, Duchenne muscular dystrophy, Edward's syndrome, EhlersDanlos syndrome, Fabry disease, fetal alcohol syndrome, Fragile X syndrome, Gilles de la Tourette syndrome, Goldenhar syndrome, Hunter's syndrome, Hurler's syndrome, Klinefelter's syndrome, LEOPARD syndrome, Moebius syndrome, Morquio's syndrome, neurofibromatosis, Niemann-Pick disease, Noonan's syndrome, osteogenesis imperfecta, Pierre-Robin syndrome, Prader-Willi syndrome, Rett's syndrome, Reye's syndrome, San Filippo syndrome, SmithMagenis syndrome, Stickler syndrome, Tay-Sachs disease, Treacher Collins syndrome, Turner's syndrome, Usher's syndrome, Waardenburg's syndrome, and William's syndrome. For each syndrome, the author lists alternative names, incidence, causation (etiology), characteristics or symptoms, management implications (treatment options), prognosis, and self-help groups to contact. Most groups listed are in England. The book

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concludes with three appendices that provide a discussion of genetics, a listing of regional genetics centers (in England), and a glossary of terms. A subject index is also included. (AA-M).

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to fragile X syndrome (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

1992 International Fragile X Conference proceedings ; ISBN: 0915667223; http://www.amazon.com/exec/obidos/ASIN/0915667223/icongroupin terna

·

Behavior and Development in Fragile X Syndrome (Developmental Clinical Psychology and Psychiatry : V.28) by Elisabeth Dykens, et al (1993); ISBN: 0803948883; http://www.amazon.com/exec/obidos/ASIN/0803948883/icongroupin terna

·

Children with Fragile X Syndrome: A Parents' Guide by Jayne Dixon Weber (Editor); ISBN: 0933149778; http://www.amazon.com/exec/obidos/ASIN/0933149778/icongroupin terna

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Fragile Sites on Human Chromosomes (Oxford Monographs on Medical Genetics, No 13) by Grant R. Sutherland, Frederick Hecht (1985); ISBN: 0195035429; http://www.amazon.com/exec/obidos/ASIN/0195035429/icongroupin terna

·

Fragile X Cancer Cytogenetics : Proceedings of the 1989 Albany Birth Defects Symposium XX (Progress in Clinical and Biological Research, Vol 368) by Ann M. Willey, Patricia D. Murphy (Editor); ISBN: 0471560987; http://www.amazon.com/exec/obidos/ASIN/0471560987/icongroupin terna

72 Fragile X Syndrome

·

Fragile X Syndrome by Randi J.\McBogg, Pam Hagerman (1983); ISBN: 0915667002; http://www.amazon.com/exec/obidos/ASIN/0915667002/icongroupin terna

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Fragile X Syndrome : Diagnosis Biochemistry & Intervention by Randi J. Hagerman, Pamela M. McBogg (1983); ISBN: 0915667010; http://www.amazon.com/exec/obidos/ASIN/0915667010/icongroupin terna

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Fragile X Syndrome: A Guide for Teachers by Suzanne Saunders; ISBN: 1853465364; http://www.amazon.com/exec/obidos/ASIN/1853465364/icongroupin terna

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Fragile X Syndrome: Diagnosis, Treatment, and Research by Randi Jenssen Hagerman (Editor), Paul J. Hagerman (Editor); ISBN: 0801868440; http://www.amazon.com/exec/obidos/ASIN/0801868440/icongroupin terna

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Fragile X Syndrome: Medical and Educational Approaches Toward Intervention by Randi, Dr Hagerman; ISBN: 1893601250; http://www.amazon.com/exec/obidos/ASIN/1893601250/icongroupin terna

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Genome Maps & Neurological Disorders (Genome Analysis Series; Vol. 6) by K. E. Davies (Editor), Shirley M. Tilghman (Editor) (1993); ISBN: 0879693878; http://www.amazon.com/exec/obidos/ASIN/0879693878/icongroupin terna

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Issues and Strategies for Educating Children With Fragile X Syndrome by Philip Wilson (1994); ISBN: 0915667231; http://www.amazon.com/exec/obidos/ASIN/0915667231/icongroupin terna

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The Fragile X Child by Betty B. Schopmeyer, Fonda Lowe (Editor) (1992); ISBN: 1879105837; http://www.amazon.com/exec/obidos/ASIN/1879105837/icongroupin terna

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The Fragile X Syndrome (Molecular Medicine) by Kay E. Davies (Editor) (1989); ISBN: 0192618369; http://www.amazon.com/exec/obidos/ASIN/0192618369/icongroupin terna

·

X-linked mental retardation : proceedings of the Workshop on the Fra(X) Form of X-linked Mental Retardation (plus supplementary papers on X-linked mental retardation and related subjects) held at the

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National Institute of Child Health and Human Development, Bethesda, Maryland, April 25 and 26, 1983 ; ISBN: 0845102346; http://www.amazon.com/exec/obidos/ASIN/0845102346/icongroupin terna ·

X-Linked Mental Retardation 2: Proceedings of the Second International Workshop on Fragile X and X-Linked Mental Retardation Held on Dunk Island, aut by John M. Opitz, et al; ISBN: 0471851582; http://www.amazon.com/exec/obidos/ASIN/0471851582/icongroupin terna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “fragile X syndrome” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:22 ·

1992 International Fragile X Conference proceedings. Author: edited by Randi Jenssen Hagerman and Pamela McKenzie; Year: 1992; Dillon, Colo.: Spectra Pub. Co., c1992; ISBN: 0915667223 http://www.amazon.com/exec/obidos/ASIN/0915667223/icongroupin terna

·

Analysis of triplet repeat disorders. Author: [edited by] D.C. Rubinsztein and M.R. Hayden; Year: 1998; Oxford ; Washington, DC: BIOS Scientific Publishers, 1998; ISBN: 1859962661 http://www.amazon.com/exec/obidos/ASIN/1859962661/icongroupin terna

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

22

74 Fragile X Syndrome

·

Development and psychopathology in fragile X syndrome. Author: Elisabeth M. Dykens, Robert M. Hodapp, James F. Leckman; Year: 1994; Thousand Oaks, Calif.: Sage Publications, c1994; ISBN: 0803948875 (cl) http://www.amazon.com/exec/obidos/ASIN/0803948875/icongroupin terna

·

Fragile sites on human chromosomes. Author: Grant R. Sutherland and Frederick Hecht, with contributions by John C. Mulley and Thomas W. Glover and Barbara K. Hecht; Year: 1985; New York: Oxford University Press, 1985; ISBN: 0195035429 http://www.amazon.com/exec/obidos/ASIN/0195035429/icongroupin terna

·

Fragile species. Author: Lewis Thomas; Year: 1992; New York: Scribner's; Toronto: Maxwell Macmillan Canada; New York: Maxwell Macmillan International, c1992; ISBN: 0684194201 http://www.amazon.com/exec/obidos/ASIN/0684194201/icongroupin terna

·

Fragile X child. Author: edited by Betty B. Schopmeyer and Fonda Lowe; Year: 1992; San Diego, Calif.: Singular Pub. Group, c1992; ISBN: 1879105837 http://www.amazon.com/exec/obidos/ASIN/1879105837/icongroupin terna

·

Fragile X syndrome: diagnosis, biochemistry, and intervention. Author: edited by Randi Jenssen Hagerman, Pamela McKenzie McBogg; Year: 1983; Dillon, Colo.: Spectra Pub. Co., c1983; ISBN: 0915667010 (pbk.) http://www.amazon.com/exec/obidos/ASIN/0915667010/icongroupin terna

·

Fragile X syndrome: diagnosis, treatment, and research. Author: edited by Randi Jenssen Hagerman and Amy Cronister; Year: 1996; Baltimore: Johns Hopkins University Press, c1996; ISBN: 0801853478 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0801853478/icongroupin terna

·

Fragile X syndrome: diagnosis, treatment, and research. Author: edited by Randi Jenssen Hagerman and Amy Cronister Silverman; Year: 1991; Baltimore: Johns Hopkins University Press, c1991; ISBN: 0801841690 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0801841690/icongroupin terna

·

Fragile X syndrome. Author: edited by Kay E. Davies; Year: 1989; Oxford; New York: Oxford University Press, 1989; ISBN: 0192618369 (pbk.)

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http://www.amazon.com/exec/obidos/ASIN/0192618369/icongroupin terna ·

Fragile X. Author: cancer cytogenetics: proceedings of the 1989 Albany Birth Defects Symposium XX, held in Albany, New York, October 16-17, 1989 / editors, Ann M. Willey, Patricia D. Murphy; Year: 1991; New York: Wiley-Liss, c1991; ISBN: 0471560987 http://www.amazon.com/exec/obidos/ASIN/0471560987/icongroupin terna

·

Insulin resistance: the metabolic syndrome X. Author: edited by Gerald M. Reaven, Ami Laws; Year: 1999; Totowa, N.J.: Humana Press, c1999; ISBN: 0896035883 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0896035883/icongroupin terna

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Mental retardation sourcebook: basic consumer health information about mental retardation and its causes: including down syndrome, fetal alcohol syndrome, fragile X syndrome, genetgic conditions, injury, and environmental sources. Author: edited by Joyce Brenn; Year: 2000; Detroit: Omnigraphics, 2000; ISBN: 0780803779 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0780803779/icongroupin terna

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X-linked mental retardation: proceedings of the Workshop on the Fra(X) Form of X-linked Mental Retardation (plus supplementary papers on X-linked mental retardation and related subjects) held at the National Institute of Child Health and Human Developmen. Author: Workshop on the Fra(X) Form of X-linked Mental Retardation (1983: National Institute of Child Health and Human Development); Year: 1984; New York: Liss, c1984; ISBN: 0845102346 http://www.amazon.com/exec/obidos/ASIN/0845102346/icongroupin terna

·

X-linked mental retardation 2. Author: John M. Opitz, editor; James F. Reynolds, associate editor; LaVelle M. Spano, assistant editor; Year: 1986; New York: Liss, c1986; ISBN: 0845142119 http://www.amazon.com/exec/obidos/ASIN/0845142119/icongroupin terna

·

X-linked mental retardation 3: proceedings of the Third International Workshop on Fragile X and X-linked Mental Retardation held in Troina, Italy, September 13-16, 1987. Author: John M. Opitz, editor, Giovanni Neri, editor; James F. Reynolds, associate editor; Year: 1988; New York: Liss, c1988; ISBN: 0845142623 http://www.amazon.com/exec/obidos/ASIN/0845142623/icongroupin terna

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Chapters on Fragile X Syndrome Frequently, fragile X syndrome will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with fragile X syndrome, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and fragile X syndrome using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “fragile X syndrome” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on fragile X syndrome: ·

Disorders of Chromosomal Origin Source: in Gerber, S.E. Etiology and Prevention of Communicative Disorders. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1998. p. 13-40. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 2386777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. Price: $65.00 plus shipping and handling. ISBN: 1565939476. Summary: This chapter on disorders of chromosomal origin is from a textbook that focuses on the primary and secondary prevention of communicative disorders. The author discusses the chromosomal system; the major chromosomal disorders, including disorders of number or structure, and disorders of sex chromosomes; and amniocentesis and prenatal diagnosis. Specific disorders covered are trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), Cri du Chat (5p-), XYY syndrome, Turner syndrome (45X), XXY (Klinefelter syndrome), and Fragile X syndrome. The author notes that although speech language pathologists and audiologists are not medical geneticists or genetic counselors, they should be familiar with chromosomal abnormalities, empathetic to patients with these conditions, and actively involved in preventive efforts. The chapter concludes with a glossary of terms and a reference list. 20 figures. 2 tables. 75 references.

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·

Fragile X Syndrome Source: in Gilbert, P. A-Z Reference Book of Syndromes and Inherited Disorders. 2nd ed. London, England: Chapman and Hall. p. 119-122. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 2386777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. Price: $42.95 plus shipping and handling. ISBN: 0412641208. Summary: This chapter on Fragile X syndrome is from a practical reference book that describes inherited disorders and syndromes in both children and adults. Fragile X syndrome is a genetic disorder that results in learning disabilities, characteristic facial features, and speech delays. There is a wide disparity in the expression of this syndrome between boys and girls; boys are more severely affected. Speech is frequently delayed during the early years. Topics include alternative names for the condition, incidence, history, causation, characteristics, management implications, prognosis, and self-help groups. The chapter concludes with a list of support groups and organizations that can be found in England.

·

Dental Problems of Children with Disabilities Source: in McDonald, R.E. and Avery, D.A., eds. Dentistry for the Child and Adolescent. 7th ed. St. Louis, MO: Mosby, Inc. 2000. p. 566-599. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. Price: $72.00 plus shipping and handling. ISBN: 0815190174. Summary: Children with disabilities may present challenges requiring special preparation before the dentist and office staff can provide acceptable care. This chapter on dental problems of children with disabilities is from a textbook on dentistry for the child and adolescent that is designed to help undergraduate dental students and postdoctoral pediatric dentistry students provide comprehensive oral health care for infants, children, teenagers, and individuals with various disabilities. The authors discuss some of the disabling conditions of children that a dentist may encounter in practice. Topics include dental access (access to health care); the first dental visit; the radiographic examination; preventive dentistry, including home dental care, diet and nutrition, fluoride exposure, and preventive restorations (pit and fissure sealants); the management of a child with disabilities during dental treatment, including treatment immobilization; and managing children with specific

78 Fragile X Syndrome

conditions including mental retardation, Down syndrome, learning disabilities, Fragile X syndrome, fetal alcohol syndrome (FAS), autism, cerebral palsy, respiratory diseases (including cystic fibrosis and asthma), hearing loss, visual impairment, and heart disease; and general dental management of medically compromised patients. 14 figures. 5 tables. 47 references. ·

Metabolic and Genetic Jaw Diseases Source: in Regezi, J.A. and Sciubba, J.J. Oral Pathology: Clinical Pathologic Correlations. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 417-452. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32821-9854. (800) 545-2522. Fax (800) 874-6418. Website: www.wbsaunders.com. Price: $63.95. ISBN: 0721677312. Summary: This chapter on metabolic and genetic jaw diseases is from a pathology textbook that presents current concepts of oral and maxillofacial pathology in order to enhance the reader's diagnostic skills through the use of differential diagnosis strategies. The text offers readers detailed guidance of etiology, pathogenesis, clinical features, histopathology, differential diagnosis, and treatment of oral diseases of the mucosa, submucosa, and bone. This chapter covers metabolic conditions, including Paget's disease, hyperparathyroidism, hyperthyroidism, hypophosphatasia, infantile cortical hyperostosis, phantom bone disease, and acromegaly; and genetic abnormalities, including cherubism, osteopetrosis, osteogenesis imperfecta, cleidocranial dysplasia, Crouzon's syndrome (craniofacial dysostosis), Treacher Collins syndrome (mandibulofacial dysostosis), Pierre Robin syndrome, Marfan's syndrome, Ehlers Danlos syndrome, Down syndrome (trisomy 21), hemifacial atrophy, hemifacial hypertrophy, clefts of the lip and palate, and Fragile X syndrome. 32 figures. 142 references.

·

Disability, the Young and the Elderly Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 470-487. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. Price: $110.00. ISBN: 0723610568.

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Summary: Disability is caused by handicapping conditions that impair normal social, educational, or recreational activities. Such patients need dental attention and treatment to at least the same standard as nonhandicapped patients; frequently this population has a greater predisposition to dental disease. This chapter on disability, the young and the elderly is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. This chapter covers only patients with mental and related handicaps, some specific conditions, children, and the elderly; patients with other important specific diseases, such as hemophilia, neurological disorders and muscular dystrophies, are covered in other chapters. Topics include learning disability, chromosomal anomalies (including Down syndrome and fragile X syndrome), thalidomide defect, hydrocephalus, cleft lip and palate, autism, the overactive child (hyperkinetic child), child abuse, selfinflicted oral lesions, juvenile delinquency, and problems in the elderly, including multiple disease, intellectual failure, social problems, drug compliance and reactions. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 appendix. 5 figures. 8 tables. 46 references.

General Home References In addition to references for fragile X syndrome, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · American Academy of Pediatrics Guide to Your Child's Symptoms : The Official, Complete Home Reference, Birth Through Adolescence by Donald Schiff (Editor), et al; Paperback - 256 pages (January 1997), Villard Books; ISBN: 0375752579; http://www.amazon.com/exec/obidos/ASIN/0375752579/icongroupinterna · The Children's Hospital Guide to Your Child's Health and Development by Alan D. Woolf (Editor), et al; Hardcover - 796 pages, 1st edition (January 15, 2001), Perseus Books; ISBN: 073820241X; http://www.amazon.com/exec/obidos/ASIN/073820241X/icongroupinterna · Helping Your Child in the Hospital: A Practical Guide for Parents by Nancy Keene, Rachel Prentice; Paperback - 176 pages, 3rd edition (April 15, 2002), O'Reilly & Associates; ISBN: 0596500114; http://www.amazon.com/exec/obidos/ASIN/0596500114/icongroupinterna

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· Medical Emergencies & Childhood Illnesses: Includes Your Child's Personal Health Journal (Parent Smart) by Penny A. Shore, William Sears (Contributor); Paperback - 115 pages (February 2002), Parent Kit Corporation; ISBN: 1896833187; http://www.amazon.com/exec/obidos/ASIN/1896833187/icongroupinterna · Taking Care of Your Child: A Parent's Guide to Complete Medical Care by Robert H. Pantell, M.D., et al; Paperback - 524 pages, 6th edition (March 5, 2002), Perseus Press; ISBN: 0738206016; http://www.amazon.com/exec/obidos/ASIN/0738206016/icongroupinterna

Vocabulary Builder Arteries: The vessels carrying blood away from the heart. [NIH] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic examination. [NIH] Chronic: Persisting over a long period of time. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Dysplasia: Abnormality of development; in pathology, alteration in size, shape, and organization of adult cells. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other health-related event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as

Books 81

dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Hydrocephalus: A condition marked by dilatation of the cerebral ventricles, most often occurring secondarily to obstruction of the cerebrospinal fluid pathways, and accompanied by an accumulation of cerebrospinal fluid within the skull; the fluid is usually under increased pressure, but occasionally may be normal or nearly so. It is typically characterized by enlargement of the head, prominence of the forehead, brain atrophy, mental deterioration, and convulsions; may be congenital or acquired; and may be of sudden onset (acute h.) or be slowly progressive (chronic or primary b.). [EU]

Hyperostosis: Hypertrophy of bone; exostosis. [EU] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Hyperthyroidism: 1. excessive functional activity of the thyroid gland. 2. the abnormal condition resulting from hyperthyroidism marked by increased metabolic rate, enlargement of the thyroid gland, rapid heart rate, high blood pressure, and various secondary symptoms. [EU] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Infantile: Pertaining to an infant or to infancy. [EU] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU]

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Midwifery: The practice of assisting women in childbirth. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Thalidomide: A pharmaceutical agent originally introduced as a nonbarbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH]

Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU]

Multimedia 83

CHAPTER 6. MULTIMEDIA ON FRAGILE X SYNDROME Overview Information on fragile X syndrome can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on fragile X syndrome. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.

Bibliography: Multimedia on Fragile X Syndrome The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in fragile X syndrome (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on fragile X syndrome. For more information, follow the hyperlink indicated: ·

Human as a model system in genetics : examples from fragile X syndrome and incontinentia pigmenti. Source: [Medical Arts and Photography Branch]; Year: 2000; Format: Videorecording; [Bethesda, Md.: National Institutes of Health, 2000]

84 Fragile X Syndrome

·

Linking medicine & education for the child with special needs. Source: [presented by] National Professional Resources; Year: 1998; Format: Videorecording; Port Chester, NY: National Professional Resources, c1998

·

Medically fragile child in the school setting : ethical issues. Source: [presented by] the Cleveland Clinic Foundation; Year: 1993; Format: Videorecording; [Cleveland, Ohio]: The Foundation, c1993

·

Medically fragile child in the school setting : legal issues. Source: [presented by] the Cleveland Clinic Foundation; Year: 1993; Format: Videorecording; [Cleveland, Ohio]: The Foundation, c1993

·

Syndromes in pediatrics. Source: Trainex Corporation; Year: 1972; Format: Filmstrip; [Garden Grove, Calif.]: Trainex, c1972

Vocabulary Builder Bronchial: Pertaining to one or more bronchi. [EU] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU]

Periodicals and News 85

CHAPTER 7. PERIODICALS AND NEWS ON FRAGILE X SYNDROME Overview Keeping up on the news relating to fragile X syndrome can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on fragile X syndrome. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover fragile X syndrome beyond and including those which are published by parent associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.

News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on fragile X syndrome is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.

86 Fragile X Syndrome

PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “fragile X syndrome” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased. The following is typical of press releases that can be found on PR Newswire: Reuters The Reuters' Medical News database can be very useful in exploring news archives relating to fragile X syndrome. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “fragile X syndrome” (or synonyms). The following was recently listed in this archive for fragile X syndrome: ·

Home environment affects cognition of children with fragile X syndrome Source: Reuters Medical News Date: March 29, 2002 http://www.reuters.gov/archive/2002/03/29/professional/links/20020 329clin016.html

·

Translational dysregulation of mRNAs associated with fragile X syndrome Source: Reuters Medical News Date: December 11, 2001 http://www.reuters.gov/archive/2001/12/11/professional/links/20011 211scie002.html

·

Fragile X syndrome may protect against cancer Source: Reuters Health eLine Date: October 25, 2001 http://www.reuters.gov/archive/2001/10/25/eline/links/20011025elin 033.html

Periodicals and News 87

·

Instrument for clinical diagnosis of fragile X syndrome in boys under development Source: Reuters Medical News Date: July 21, 2000 http://www.reuters.gov/archive/2000/07/21/professional/links/20000 721clin003.html

·

3-D Structure Of The Fragile X Syndrome Protein Revealed Source: Reuters Medical News Date: August 27, 1997 http://www.reuters.gov/archive/1997/08/27/professional/links/19970 827scie001.html

·

Fragile X Syndrome Linked To Impaired Synaptic Development In Mice Source: Reuters Medical News Date: May 14, 1997 http://www.reuters.gov/archive/1997/05/14/professional/links/19970 514scie001.html The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within their search engine.

Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com. You can scan the news by industry category or company name.

Internet Wire Internet Wire is more focused on technology than the other wires. To access this site, go to http://www.internetwire.com and use the “Search Archive” option. Type in “fragile X syndrome” (or synonyms). As this service is

88 Fragile X Syndrome

oriented to technology, you may wish to search for press releases covering diagnostic procedures or tests that you may have read about.

Search Engines Free-to-view news can also be found in the news section of your favorite search engines (see the health news page at Yahoo: http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “fragile X syndrome” (or synonyms). If you know the name of a company that is relevant to fragile X syndrome, you can go to any stock trading Web site (such as www.etrade.com) and search for the company name there. News items across various news sources are reported on indicated hyperlinks.

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “fragile X syndrome” (or synonyms).

Newsletters on Fragile X Syndrome Given their focus on current and relevant developments, newsletters are often more useful to parents than academic articles. You can find newsletters using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Your investigation must limit the search to “Newsletter” and “fragile X syndrome.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” By making these selections and typing in “fragile X syndrome” or synonyms into the “For these words:” box, you will only receive results on newsletters. The following list was generated using the options described above: ·

FRAXA Research Foundation, Inc. Newsletter Source: West Newbury, MA: FRAXA Research Foundation, Inc. 1995. [8 p. average].

Periodicals and News 89

Contact: Available from FRAXA Research Foundation, Inc. P.O. Box 935, West Newbury, MA 01985. (508) 462-1990. PRICE: Free with membership. Summary: This newsletter is intended for members of the FRAXA Research Foundation, an voluntary organization run by parents of children with fragile X syndrome. A typical issue includes foundation news and announcements, research and treatment updates, genetic research projects, publication reviews, and previews of upcoming programs and fundraising activities.

Academic Periodicals covering Fragile X Syndrome Academic periodicals can be a highly technical yet valuable source of information on fragile X syndrome. We have compiled the following list of periodicals known to publish articles relating to fragile X syndrome and which are currently indexed within the National Library of Medicine's PubMed database (follow hyperlinks to view more information, summaries, etc., for each). In addition to these sources, to keep current on articles written on fragile X syndrome published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical's name into the search box to find the latest studies published. If you want complete details about the historical contents of a periodical, you can also visit http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/ you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.” The following is a sample of periodicals which publish articles on fragile X syndrome: ·

Brain Research. (Brain Res) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Br ain+Research&dispmax=20&dispstart=0

90 Fragile X Syndrome

Vocabulary Builder Abdominal: Pertaining to the abdomen. [EU] Absenteeism: Chronic absence from work or other duty. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Constipation: Infrequent or difficult evacuation of the faeces. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU]

Physician Guidelines and Databases 91

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help children with fragile X syndrome. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common medical conditions, the National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

92 Fragile X Syndrome

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.23 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:24 ·

Bioethics: Access to published literature on the ethical, legal and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

·

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

·

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

·

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

·

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

·

Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 24 See http://www.nlm.nih.gov/databases/databases.html. 23

Physician Guidelines and Databases 93

·

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

·

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

·

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

·

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

·

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

·

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

·

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

While all of the above references may be of interest to physicians who study and treat fragile X syndrome, the following are particularly noteworthy.

94 Fragile X Syndrome

The Combined Health Information Database A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and fragile X syndrome using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years,” select your preferred language, and the format option “Fact Sheet.” By making these selections and typing “fragile X syndrome” (or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with fragile X syndrome. The following is a sample result: ·

A Fragile Xplanation Source: Madison, WI: Great Lakes Regional Genetics Group, University of Madison-Wisconsin . 1997. 8 pp. Contact: Available from National Maternal and Child Health Clearinghouse, 2070 Chain Bridge Road, Suite 450, Vienna, VA 221822536. Telephone: (703) 356-1964 or (888) 434-4MCH / fax: (703) 821-2098 / e-mail: [email protected] / Web site: http://www.nmchc.org. Available at no charge. Summary: This brochure gives a brief explanation of Fragile X syndrome. It designed to be given to parents undergoing genetic counseling and who are considering molecular testing for the syndrome. [Funded by the Maternal and Child Health Bureau].

The NLM Gateway25 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing “one-stop searching” for many of NLM's information resources or databases.26 One target audience for the Gateway is the Internet user who is new to NLM's online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

25 26

Physician Guidelines and Databases 95

researchers, librarians, students, and, increasingly, parents and the public.27 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “fragile X syndrome” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Items Found Journal Articles 2515 Books / Periodicals / Audio Visual 26 Consumer Health 20 Meeting Abstracts 2 Other Collections 1 Total 2564

Other users may find the Gateway useful for an overall search of NLM's information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 27

96 Fragile X Syndrome

HSTAT28 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.29 HSTAT's audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ's Put Prevention Into Practice.30 Simply search by “fragile X syndrome” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists31 Some parents may wish to have access to a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. To this end, we recommend “Coffee Break,” a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.32 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.33 This site has new Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. The HSTAT URL is http://hstat.nlm.nih.gov/. 30 Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 31 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 32 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 33 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 28 29

Physician Guidelines and Databases 97

articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. Access the Coffee Break Web site at http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are a few examples that may interest you: ·

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

·

Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center's MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.

·

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

·

MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.

·

Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see the following Web site: http://www.lexical.com/Metaphrase.html.

The Genome Project and Fragile X Syndrome With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and parents want to know about how human genes relate to fragile X syndrome. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.

98 Fragile X Syndrome

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).34 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI's Entrez database of MEDLINE articles and sequence information. Go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html to search the database. Type “fragile X syndrome” (or synonyms) in the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for fragile X syndrome: ·

Siderius X-linked Mental Retardation Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?300263

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

34

Physician Guidelines and Databases 99

Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to re-visit it from time to time. The following systems and associated disorders are addressed: ·

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn's disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

·

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, Atherosclerosis, Best disease, Gaucher disease, Glucose galactose malabsorption, Gyrate atrophy, Juvenile onset diabetes, Obesity, Paroxysmal nocturnal hemoglobinuria, Phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

·

Nervous System: Mind and body. Examples: Alzheimer disease, Amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, Fragile X syndrome, Friedreich's ataxia, Huntington disease, NiemannPick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, Spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

·

Signals: Cellular messages. Examples: Ataxia telangiectasia, Baldness, Cockayne syndrome, Glaucoma, SRY: sex determination, Tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

·

Transporters: Pumps and channels. Examples: Cystic Fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson's disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html

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Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

·

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

·

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

·

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

·

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

·

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

·

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

·

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

·

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

·

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

NCBI's Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/, and then select the database that you would like to search. The databases available are listed in

Physician Guidelines and Databases 101

the drop box next to “Search.” In the box next to “for,” enter “fragile X syndrome” (or synonyms) and click “Go.”

Jablonski's Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database35 This online resource can be quite useful. It has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html you can also search across syndromes using an alphabetical index. You can also search at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database36 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB's mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “fragile X syndrome” (or synonyms) into the search box, and review the Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 36 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission. 35

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results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to nonprofessionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.

Specialized References The following books are specialized references written for professionals interested in fragile X syndrome (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Atlas of Pediatric Physical Diagnosis by Basil J. Zitelli, Holly W. Davis (Editor); Hardcover, 3rd edition (March 1997), Mosby-Year Book; ISBN: 0815199309; http://www.amazon.com/exec/obidos/ASIN/0815199309/icongroupinterna · The 5-Minute Pediatric Consult by M. William Schwartz (Editor); Hardcover - 1050 pages, 2nd edition (January 15, 2000), Lippincott, Williams & Wilkins; ISBN: 0683307444; http://www.amazon.com/exec/obidos/ASIN/0683307444/icongroupinterna · Nelson Textbook of Pediatrics by Richard E. Behrman (Editor), et al; Hardcover - 2414 pages, 16th edition (January 15, 2000), W B Saunders Co; ISBN: 0721677673; http://www.amazon.com/exec/obidos/ASIN/0721677673/icongroupinterna

Dissertations 103

CHAPTER 9. DISSERTATIONS ON FRAGILE X SYNDROME Overview University researchers are active in studying almost all known medical conditions. The result of research is often published in the form of Doctoral or Master's dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to fragile X syndrome. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.

Dissertations on Fragile X Syndrome ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to fragile X syndrome. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with fragile X syndrome: ·

A Longitudinal Investigation of Family Needs: Mothers of Children with Fragile X Syndrome by Beck, Melissa Queen Hargett; Phd from The University of North Carolina at Chapel Hill, 2000, 88 pages http://wwwlib.umi.com/dissertations/fullcit/9979424

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·

An Investigation into the Academic Profile of Girls Affected by Fragile X Syndrome (genetic Disorders) by Ingram, Ellen M., Edd from University of Northern Colorado, 1991, 120 pages http://wwwlib.umi.com/dissertations/fullcit/9216420

·

Fragile X Syndrome and Early Communication Development by Mckenna, Patricia; Phd from Vanderbilt University, 2000, 140 pages http://wwwlib.umi.com/dissertations/fullcit/9970060

·

Fragile X Syndrome: Historical Overview of a Unique X-linked Disorder by Smith, Kara Marie; Ms from Sarah Lawrence College, 2000, 31 pages http://wwwlib.umi.com/dissertations/fullcit/1398890

·

Studies toward an Understanding of the Pleiotropic Nature of Fragile X Syndrome by Kenneson, Aileen Ann; Phd from Emory University, 2000, 200 pages http://wwwlib.umi.com/dissertations/fullcit/9993465

·

The Role of Temperament and Emotion Regulation in the Social Adjustment of Children with Fragile X Syndrome and Down Syndrome by Urv, Tiina Karin, Phd from Columbia University, 1998, 206 pages http://wwwlib.umi.com/dissertations/fullcit/9910672

Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to fragile X syndrome is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.

105

PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics relating to fragile X syndrome and related conditions.

Researching Your Child’s Medications 107

APPENDIX A. RESEARCHING YOUR CHILD’S MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to treat fragile X syndrome. While a number of hard copy or CD-Rom resources are available to parents and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your child’s medications. You may also want to research medications that your child is currently taking for other conditions as they may interact with medications for fragile X syndrome. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of fragile X syndrome. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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Your Child’s Medications: The Basics37 The Agency for Health Care Research and Quality has published extremely useful guidelines on the medication aspects of fragile X syndrome. Giving your child medication can involve many steps and decisions each day. The AHCRQ recommends that parents take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions, your child may be spared from possible problems. Here are some points to cover each time a new medicine is prescribed: ·

Ask about all parts of your child’s treatment, including diet changes, exercise, and medicines.

·

Ask about the risks and benefits of each medicine or other treatment your child might receive.

·

Ask how often you or your child’s doctor will check for side effects from a given medication.

Do not hesitate to tell the doctor about preferences you have for your child’s medicines. You may want your child to have a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost. Or, you may want the medicine the doctor believes will work the best. Sharing your concerns will help the doctor select the best treatment for your child. Do not be afraid to “bother” the doctor with your questions about medications for fragile X syndrome. You can also talk to a nurse or a pharmacist. They can help you better understand your child’s treatment plan. Talking over your child’s options with someone you trust can help you make better choices. Specifically, ask the doctor the following: ·

The name of the medicine and what it is supposed to do.

·

How and when to give your child the medicine, how much, and for how long.

·

What food, drinks, other medicines, or activities your child should avoid while taking the medicine.

·

What side effects your child may experience, and what to do if they occur.

·

If there are any refills, and how often.

·

About any terms or directions you do not understand.

·

What to do if your child misses a dose.

37

This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.

Researching Your Child’s Medications 109

·

If there is written information you can take home (most pharmacies have information sheets on prescription medicines; some even offer large-print or Spanish versions).

Do not forget to tell the doctor about all the medicines your child is currently taking (not just those for fragile X syndrome). This includes prescription medicines and the medicines that you buy over the counter. When talking to the doctor, you may wish to prepare a list of medicines your child is currently taking including why and in what forms. Be sure to include the following information for each: ·

Name of medicine

·

Reason taken

·

Dosage

·

Time(s) of day

Also include any over-the-counter medicines, such as: ·

Laxatives

·

Diet pills

·

Vitamins

·

Cold medicine

·

Aspirin or other pain, headache, or fever medicine

·

Cough medicine

·

Allergy relief medicine

·

Antacids

·

Sleeping pills

·

Others (include names)

Learning More about Your Child’s Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications the doctor has recommended for fragile X syndrome. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the “U.S. Pharmacopeia (USP).” Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state

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associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration's (FDA) Drug Approvals database.38 While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopoeia. It is important to read the disclaimer by the United States Pharmacopoeia (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided.

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. You may be able to access these sources from your local medical library or your child’s doctor's office.

Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html.

Mosby's GenRx Mosby's GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides information on prescribing and drug interactions. Information in Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.

38

Researching Your Child’s Medications 111

Mosby's GenRx database can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html.

Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.

Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.

Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for children with fragile X syndrome--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat fragile X syndrome or potentially create deleterious side effects in patients with fragile X syndrome. You should ask the physician about any contraindications, especially as these might apply to other medications that your child may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause your child to experience an unexpected side effect. Drug interactions may make medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to your child. Be sure to read the label every time you give your child a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your child’s health. You can reduce the risk of

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potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes avaiable. This is why it's especially important to read the label every time you give your child a medication. When the doctor prescribes a new drug, discuss all overthe-counter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals your child takes. Ask your pharmacist for the package insert for each drug prescribed. The package insert provides more information about potential drug interactions.

A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for fragile X syndrome. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt your child. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with fragile X syndrome. The FDA warns to watch out for39: ·

Secret formulas (real scientists share what they know)

·

Amazing breakthroughs or miracle cures (real breakthroughs don't happen very often; when they do, real scientists do not call them amazing or miracles)

·

Quick, painless, or guaranteed cures

·

If it sounds too good to be true, it probably isn't true.

If you have any questions about any kind of medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.

39

Researching Your Child’s Medications 113

General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Complete Guide to Prescription and Nonprescription Drugs 2001 (Complete Guide to Prescription and Nonprescription Drugs, 2001) by H. Winter Griffith, Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/039952634X/icongroupinterna

·

The Essential Guide to Prescription Drugs, 2001 by James J. Rybacki, James W. Long; Paperback - 1274 pages (2001), Harper Resource; ISBN: 0060958162; http://www.amazon.com/exec/obidos/ASIN/0060958162/icongroupinterna

·

Handbook of Commonly Prescribed Drugs by G. John Digregorio, Edward J. Barbieri; Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/0942447417/icongroupinterna

·

Johns Hopkins Complete Home Encyclopedia of Drugs 2nd ed. by Simeon Margolis (Ed.), Johns Hopkins; Hardcover - 835 pages (2000), Rebus; ISBN: 0929661583; http://www.amazon.com/exec/obidos/ASIN/0929661583/icongroupinterna

·

Medical Pocket Reference: Drugs 2002 by Springhouse Paperback 1st edition (2001), Lippincott Williams & Wilkins Publishers; ISBN: 1582550964; http://www.amazon.com/exec/obidos/ASIN/1582550964/icongroupinterna

·

PDR by Medical Economics Staff, Medical Economics Staff Hardcover 3506 pages 55th edition (2000), Medical Economics Company; ISBN: 1563633752; http://www.amazon.com/exec/obidos/ASIN/1563633752/icongroupinterna

·

Pharmacy Simplified: A Glossary of Terms by James Grogan; Paperback 432 pages, 1st edition (2001), Delmar Publishers; ISBN: 0766828581; http://www.amazon.com/exec/obidos/ASIN/0766828581/icongroupinterna

·

Physician Federal Desk Reference by Christine B. Fraizer; Paperback 2nd edition (2001), Medicode Inc; ISBN: 1563373971; http://www.amazon.com/exec/obidos/ASIN/1563373971/icongroupinterna

·

Physician's Desk Reference Supplements Paperback - 300 pages, 53 edition (1999), ISBN: 1563632950; http://www.amazon.com/exec/obidos/ASIN/1563632950/icongroupinterna

Researching Alternative Medicine 115

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your child’s doctor or your friends have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to fragile X syndrome. Finally, at the conclusion of this chapter, we will provide a list of readings on fragile X syndrome from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine's (NCCAM) overview of complementary and alternative medicine.

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What Is CAM?40 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also known as “preventive,” which means that the practitioner educates and treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.

What Are the Domains of Alternative Medicine?41 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy 40 41

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is. Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.

Researching Alternative Medicine 117

therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each. Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and illness, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India's traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body's defense mechanisms and healing processes in order to treat illness.

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Naturopathic medicine is based on the theory that a medical condition is the manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than treatment for the condition itself. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.

Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind's capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing. Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine's use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat medical conditions with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory conditions.

Researching Alternative Medicine 119

Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body's systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues. Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects recovery and that healing is promoted when the body's energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.

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Can Alternatives Affect My Child’s Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your child’s medical treatment. It becomes all the more important to speak with the doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for everyone.42 Is It Okay to Want Both Traditional and Alternative Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your child’s healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires that the practitioner know of all conventional and alternative therapies that your child is taking. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.

Finding CAM References on Fragile X Syndrome Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for fragile X syndrome. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required.

The Combined Health Information Database For a targeted search, The Combined Health Information Database is a bibliographic database produced by health-related agencies of the Federal 42

Adapted from http://www.4woman.gov/faq/alternative.htm.

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Government (mostly from the National Institutes of Health). This database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “fragile X syndrome” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: ·

Nutritional Treatments for Autism Source: Townsend Letter for Doctors and Patients. (No. 180): 58. July 1998. Summary: This journal article describes some nutritional treatments that may benefit children with autism. Vitamin B6 supplementation has been shown to improve behavior and normalize abnormal electrophysiological and biochemical measures in autistic children. Magnesium usually is added to vitamin B6 to prevent magnesium depletion, irritability, sound hypersensitivity, and enuresis that sometimes follow vitamin B6 supplementation. One study found that a behavioral improvement occurred only when the two nutrients were given together, and of the more than a dozen research studies, all have reported positive outcomes. Supplementation with folate also has shown benefits in a subgroup of autistic patients. In one study, boys with fragile X syndrome showed improvement in their behavior and motor ability after receiving folate supplements, whereas adult males showed no change. Finally, removing certain foods from the diet may help some autistic patients who are foodsensitive. The article has 11 references.

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National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov) has created a link to the National Library of Medicine's databases to allow parents to search for articles that specifically relate to fragile X syndrome and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “fragile X syndrome” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to fragile X syndrome: ·

Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome. Author(s): Nielsen DM, Derber WJ, McClellan DA, Crnic LS. Source: Brain Research. 2002 February 8; 927(1): 8-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11814427&dopt=Abstract

·

Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Author(s): Musumeci SA, Bosco P, Calabrese G, Bakker C, De Sarro GB, Elia M, Ferri R, Oostra BA. Source: Epilepsia. 2000 January; 41(1): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10643918&dopt=Abstract

·

Fragile X mice develop sensory hyperreactivity to auditory stimuli. Author(s): Chen L, Toth M. Source: Neuroscience. 2001; 103(4): 1043-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11301211&dopt=Abstract

·

Fragile X syndrome. Author(s): Gelbart M. Source: Nurs Times. 1998 November 25-December 1; 94(47): 45. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9934149&dopt=Abstract

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·

High dose folic acid treatment of fragile (X) males. Author(s): Brown WT, Cohen IL, Fisch GS, Wolf-Schein EG, Jenkins VA, Malik MN, Jenkins EC. Source: American Journal of Medical Genetics. 1986 January-February; 23(1-2): 263-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3513568&dopt=Abstract

·

Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P. Author(s): Tamanini F, Van Unen L, Bakker C, Sacchi N, Galjaard H, Oostra BA, Hoogeveen AT. Source: The Biochemical Journal. 1999 November 1; 343 Pt 3: 517-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10527928&dopt=Abstract

·

Spatial learning, contextual fear conditioning and conditioned emotional response in Fmr1 knockout mice. Author(s): Van Dam D, D'Hooge R, Hauben E, Reyniers E, Gantois I, Bakker CE, Oostra BA, Kooy RF, De Deyn PP. Source: Behavioural Brain Research. 2000 December 20; 117(1-2): 127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11099766&dopt=Abstract

·

The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. Author(s): Eberhart DE, Malter HE, Feng Y, Warren ST. Source: Human Molecular Genetics. 1996 August; 5(8): 1083-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8842725&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

·

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

·

Chinese Medicine: http://www.newcenturynutrition.com/

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·

drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html

·

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

·

Google: http://directory.google.com/Top/Health/Alternative/

·

Healthnotes: http://www.thedacare.org/healthnotes/

·

Open Directory Project: http://dmoz.org/Health/Alternative/

·

TPN.com: http://www.tnp.com/

·

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

·

WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

·

WellNet: http://www.wellnet.ca/herbsa-c.htm

·

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): ·

Healthy Child, Whole Child: Integrating the Best of Conventional and Alternative Medicine to Keep Your Kids Healthy by Stuart H. Ditchek, M.D. and Russell H. Greenfield; Paperback - 464 pages (June 2002), Harper Resource; ISBN: 0062737465; http://www.amazon.com/exec/obidos/ASIN/0062737465/icongroupinterna

·

Alternative Medicine for Dummies by James Dillard (Author); Audio Cassette, Abridged edition (1998), Harper Audio; ISBN: 0694520659; http://www.amazon.com/exec/obidos/ASIN/0694520659/icongroupinterna

·

Complementary and Alternative Medicine Secrets by W. Kohatsu (Editor); Hardcover (2001), Hanley & Belfus; ISBN: 1560534400; http://www.amazon.com/exec/obidos/ASIN/1560534400/icongroupinterna

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·

Dictionary of Alternative Medicine by J. C. Segen; Paperback-2nd edition (2001), Appleton & Lange; ISBN: 0838516211; http://www.amazon.com/exec/obidos/ASIN/0838516211/icongroupinterna

·

Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating by Walter C. Willett, MD, et al; Hardcover - 352 pages (2001), Simon & Schuster; ISBN: 0684863375; http://www.amazon.com/exec/obidos/ASIN/0684863375/icongroupinterna

· Encyclopedia of Natural Medicine, Revised 2nd Edition by Michael T. Murray, Joseph E. Pizzorno; Paperback - 960 pages, 2nd Rev edition (1997), Prima Publishing; ISBN: 0761511571; http://www.amazon.com/exec/obidos/ASIN/0761511571/icongroupinterna ·

Integrative Medicine: An Introduction to the Art & Science of Healing by Andrew Weil (Author); Audio Cassette, Unabridged edition (2001), Sounds True; ISBN: 1564558541; http://www.amazon.com/exec/obidos/ASIN/1564558541/icongroupinterna

·

New Encyclopedia of Herbs & Their Uses by Deni Bown; Hardcover - 448 pages, Revised edition (2001), DK Publishing; ISBN: 078948031X; http://www.amazon.com/exec/obidos/ASIN/078948031X/icongroupinterna

· Textbook of Complementary and Alternative Medicine by Wayne B. Jonas; Hardcover (2003), Lippincott, Williams & Wilkins; ISBN: 0683044370; http://www.amazon.com/exec/obidos/ASIN/0683044370/icongroupinterna For additional information on complementary and alternative medicine, ask your child’s doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU]

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Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bedwetting, nocturnal enuresis). [EU] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU]

Researching Nutrition 127

APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements for fragile X syndrome. Any dietary recommendation is based on age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with fragile X syndrome may be given different recommendations. Some recommendations may be directly related to fragile X syndrome, while others may be more related to general health. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of fragile X syndrome. We will then show you how to find studies dedicated specifically to nutrition and fragile X syndrome.

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Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·

Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.

·

Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.

·

Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.

·

Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.

Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your child’s diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·

Vitamin A is important to the health of eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.

·

Vitamin B1, also known as thiamine, is important for the nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.

·

Vitamin B2, also known as riboflavin, is important for the nervous system and muscles, but is also involved in the release of proteins from

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nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs. ·

Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains

·

Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.

·

Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.

·

Vitamin C allows the body's immune system to fight various medical conditions, strengthens body tissue, and improves the body's use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.

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Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.

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Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.

·

Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.

·

Folic Acid maintains healthy cells and blood; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.

It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·

Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.

·

Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.

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·

Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.

·

Iodine helps regulate the body's use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.

·

Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.

·

Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.

·

Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.

·

Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.

·

Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.

The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, the doctor may encourage deviations from the average official recommendation based on your child’s specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/lab-cons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:43 ·

DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.

·

DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.

43

Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.

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·

RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.”

·

RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?44

Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”45 According to the ODS, dietary supplements can have an important impact on the prevention and management of medical conditions and on the maintenance of health.46 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where the use of plant products, in particular, has a long tradition. However, the This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 45 Contact: The Office of Dietary Supplements, National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: (301) 435-2920, Fax: (301) 480-1845, E-mail: [email protected]. 46 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 44

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overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of Dietary Supplements National Institutes of Health Building 31, Room 1B29 31 Center Drive, MSC 2086 Bethesda, Maryland 20892-2086 Tel: (301) 435-2920 Fax: (301) 480-1845 E-mail: [email protected]

Finding Studies on Fragile X Syndrome The NIH maintains an office dedicated to nutrition and diet. The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.47 IBIDS is available to the public free of charge through the ODS Internet page: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back periodically as this database is frequently updated. More studies can be Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

47

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found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “fragile X syndrome” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following information is typical of that found when using the “Full IBIDS Database” when searching using “fragile X syndrome” (or a synonym): ·

Cyclic AMP metabolism in fragile X syndrome. Author(s): Department of Pediatrics, University of Chicago, IL. Source: Berry Kravis, E Huttenlocher, P R Ann-Neurol. 1992 January; 31(1): 22-6 0364-5134

·

Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. Author(s): Department of Obstetrics and Gynecology, Illinois Masonic Medical Center, Chicago 60657. Source: Strom, C M Brusca, R M Pizzi, W J Am-J-Med-Genet. 1992 November 15; 44(5): 676-82 0148-7299

·

Fragile X syndrome. Author(s): University of Wisconsin, Madison. Source: Laxova, R Adv-Pediatr. 1994; 41305-42 0065-3101

·

Picture of the month. Fragile X syndrome. Author(s): Department of Pediatrics, University of Calgary, Children's Hospital, Alberta. Source: Leung, A K McLeod, D R Robson, W L Fagan, J E Arch-PediatrAdolesc-Med. 1994 January; 148(1): 63-4 1072-4710

·

Screening for fragile X syndrome: information needs for health planners. Author(s): Centre for Reproduction, Growth & Development, Research School of Medicine, University of Leeds, United Kingdom. Source: Murray, J Cuckle, H Taylor, G Hewison, J J-Med-Screen. 1997; 4(2): 60-94 0969-1413

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA)

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provide many sources of information on general nutrition and health. Recommended resources include: ·

healthfinder®, HHS's gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

·

The United States Department of Agriculture's Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration's Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

·

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

·

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

·

Google: http://directory.google.com/Top/Health/Nutrition/

·

Healthnotes: http://www.thedacare.org/healthnotes/

·

Open Directory Project: http://dmoz.org/Health/Nutrition/

·

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

·

WebMDÒHealth: http://my.webmd.com/nutrition

·

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

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Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Riboflavin:

Nutritional factor found in milk, eggs, malted barley, liver,

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kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH]

Finding Medical Libraries 137

APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, your local public library and medical libraries have Interlibrary Loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. NLM's interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.48

48

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located):49 ·

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

·

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM

·

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

·

California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html

·

California: Community Health Library of Los Gatos (Community Health Library of Los Gatos), http://www.healthlib.org/orgresources.html

·

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

·

California: Gateway Health Library (Sutter Gould Medical Foundation)

·

California: Health Library (Stanford University Medical Center), http://www-med.stanford.edu/healthlibrary/

49

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 139

·

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

·

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

·

California: San José PlaneTree Health Library, http://planetreesanjose.org/

·

California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html

·

California: University of California, Davis. Health Sciences Libraries

·

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html

·

California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm

·

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

·

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

·

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

·

Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/

140 Fragile X Syndrome

·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm

·

Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/

·

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/

·

Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/

·

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm

·

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/

·

Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library

·

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10

·

Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html

·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml

Finding Medical Libraries 141

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

·

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

·

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://medlibwww.bu.edu/library/lib.html

·

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

·

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke's Hospital Health Sciences Library (St. Luke's Hospital), http://www.southcoast.org/library/

·

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

·

Massachusetts: UMass HealthNet (University of Massachusetts Medical School), http://healthnet.umassmed.edu/

·

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

·

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

·

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41

142 Fragile X Syndrome

·

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

·

National: National Network of Libraries of Medicine (National Library of Medicine) - provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

·

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

·

Nevada: Health Science Library, West Charleston Library (Las Vegas Clark County Library District), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

·

New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm

·

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center), http://www.geocities.com/ResearchTriangle/9360/

·

New York: Choices in Health Information (New York Public Library) NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

·

New York: Health Information Center (Upstate Medical University, State University of New York), http://www.upstate.edu/library/hic/

·

New York: Health Sciences Library (Long Island Jewish Medical Center), http://www.lij.edu/library/library.html

·

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

·

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

·

Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp

Finding Medical Libraries 143

·

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/

·

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml

·

Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html

·

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.html

·

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

·

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System), http://www.shscares.org/services/lrc/index.asp

·

Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/

·

South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Texas: Matustik Family Resource Center (Cook Children's Health Care System), http://www.cookchildrens.com/Matustik_Library.html

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/

Your Child’s Rights and Insurance 145

APPENDIX E. YOUR CHILD’S RIGHTS AND INSURANCE Overview Parents face a series of issues related more to the healthcare industry than to their children’s medical conditions. This appendix covers two important topics in this regard: your responsibilities and your child’s rights as a patient, and how to get the most out of your child’s medical insurance plan.

Your Child’s Rights as a Patient The President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has created the following summary of your child’s rights as a patient.50

50Adapted

from Consumer Bill of Rights and Responsibilities: http://www.hcqualitycommission.gov/press/cbor.html#head1.

146 Fragile X Syndrome

Information Disclosure Consumers have the right to receive accurate, easily understood information. Some consumers require assistance in making informed decisions about health plans, health professionals, and healthcare facilities. Such information includes: ·

Health plans. Covered benefits, cost-sharing, and procedures for resolving complaints, licensure, certification, and accreditation status, comparable measures of quality and consumer satisfaction, provider network composition, the procedures that govern access to specialists and emergency services, and care management information.

·

Health professionals. Education, board certification, and recertification, years of practice, experience performing certain procedures, and comparable measures of quality and consumer satisfaction.

·

Healthcare facilities. Experience in performing certain procedures and services, accreditation status, comparable measures of quality, worker, and consumer satisfaction, and procedures for resolving complaints.

·

Consumer assistance programs. Programs must be carefully structured to promote consumer confidence and to work cooperatively with health plans, providers, payers, and regulators. Desirable characteristics of such programs are sponsorship that ensures accountability to the interests of consumers and stable, adequate funding.

Choice of Providers and Plans Consumers have the right to a choice of healthcare providers that is sufficient to ensure access to appropriate high-quality healthcare. To ensure such choice, the Commission recommends the following: ·

Provider network adequacy. All health plan networks should provide access to sufficient numbers and types of providers to assure that all covered services will be accessible without unreasonable delay -including access to emergency services 24 hours a day and 7 days a week. If a health plan has an insufficient number or type of providers to provide a covered benefit with the appropriate degree of specialization, the plan should ensure that the consumer obtains the benefit outside the network at no greater cost than if the benefit were obtained from participating providers.

·

Access to specialists. Consumers with complex or serious medical conditions who require frequent specialty care should have direct access

Your Child’s Rights and Insurance 147

to a qualified specialist of their choice within a plan's network of providers. Authorizations, when required, should be for an adequate number of direct access visits under an approved treatment plan. ·

Transitional care. Consumers who are undergoing a course of treatment for a chronic or disabling condition at the time they involuntarily change health plans or at a time when a provider is terminated by a plan for other than cause should be able to continue seeing their current specialty providers for up to 90 days to allow for transition of care.

·

Choice of health plans. Public and private group purchasers should, wherever feasible, offer consumers a choice of high-quality health insurance plans. Access to Emergency Services

Consumers have the right to access emergency healthcare services when and where the need arises. Health plans should provide payment when a consumer presents to an emergency department with acute symptoms of sufficient severity--including severe pain--such that a “prudent layperson” could reasonably expect the absence of medical attention to result in placing that consumer's health in serious jeopardy, serious impairment to bodily functions, or serious dysfunction of any bodily organ or part.

Participation in Treatment Decisions Consumers have the right and responsibility to fully participate in all decisions related to their healthcare. Consumers who are unable to fully participate in treatment decisions have the right to be represented by parents, guardians, family members, or other conservators. Physicians and other health professionals should: ·

Provide parents with sufficient information and opportunity to decide among treatment options consistent with the informed consent process.

·

Discuss all treatment options with a parent in a culturally competent manner, including the option of no treatment at all.

·

Ensure that persons with disabilities have effective communications with members of the health system in making such decisions.

·

Discuss all current treatments a consumer may be undergoing.

·

Discuss all risks, nontreatment.

benefits,

and

consequences

to

treatment

or

148 Fragile X Syndrome

·

Give parents the opportunity to refuse treatment for their children and to express preferences about future treatment decisions.

·

Discuss the use of advance directives -- both living wills and durable powers of attorney for healthcare -- with parents.

·

Abide by the decisions made by parents consistent with the informed consent process.

Health plans, health providers, and healthcare facilities should: ·

Disclose to consumers factors -- such as methods of compensation, ownership of or interest in healthcare facilities, or matters of conscience -that could influence advice or treatment decisions.

·

Assure that provider contracts do not contain any so-called “gag clauses” or other contractual mechanisms that restrict healthcare providers' ability to communicate with and advise parents about medically necessary treatment options for their children.

·

Be prohibited from penalizing or seeking retribution against healthcare professionals or other health workers for advocating on behalf of their patients. Respect and Nondiscrimination

Consumers have the right to considerate, respectful care from all members of the healthcare industry at all times and under all circumstances. An environment of mutual respect is essential to maintain a quality healthcare system. To assure that right, the Commission recommends the following: ·

Consumers must not be discriminated against in the delivery of healthcare services consistent with the benefits covered in their policy, or as required by law, based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.

·

Consumers eligible for coverage under the terms and conditions of a health plan or program, or as required by law, must not be discriminated against in marketing and enrollment practices based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.

Your Child’s Rights and Insurance 149

Confidentiality of Health Information Consumers have the right to communicate with healthcare providers in confidence and to have the confidentiality of their individually identifiable healthcare information protected. Consumers also have the right to review and copy their own medical records and request amendments to their records.

Complaints and Appeals Consumers have the right to a fair and efficient process for resolving differences with their health plans, healthcare providers, and the institutions that serve them, including a rigorous system of internal review and an independent system of external review. A free copy of the Patient's Bill of Rights is available from the American Hospital Association.51

Parent Responsibilities To underscore the importance of finance in modern healthcare as well as your responsibility for the financial aspects of your child’s care, the President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has proposed that parents understand the following “Consumer Responsibilities.”52 In a healthcare system that protects consumers' rights, it is reasonable to expect and encourage consumers to assume certain responsibilities. Greater involvement by parents in their children’s care increases the likelihood of achieving the best outcome and helps support a quality-oriented, cost-conscious environment. Such responsibilities include: ·

Take responsibility for maximizing your child’s healthy habits.

·

Work collaboratively with healthcare providers in developing and carrying out your child’s agreed-upon treatment plans.

·

Disclose relevant information and clearly communicate wants and needs.

51 To order your free copy of the Patient's Bill of Rights, telephone 312-422-3000 or visit the American Hospital Association’s Web site: http://www.aha.org. Click on “Resource Center,” go to “Search” at bottom of page, and then type in “Patient's Bill of Rights.” The Patient’s Bill of Rights is also available from Fax on Demand, at 312-422-2020, document number 471124. 52 Adapted from http://www.hcqualitycommission.gov/press/cbor.html#head1.

150 Fragile X Syndrome

·

Use the insurance company's internal complaint and appeal processes to address your concerns.

·

Recognize the reality of risks, the limits of the medical science, and the human fallibility of the healthcare professional.

·

Be aware of a healthcare provider's obligation to be reasonably efficient and equitable in providing care to the community.

·

Become knowledgeable about health plan coverage and options (when available) including all covered benefits, limitations, and exclusions, rules regarding use of network providers, coverage and referral rules, appropriate processes to secure additional information, and the process to appeal coverage decisions.

·

Make a good-faith effort to meet financial obligations.

·

Abide by administrative and operational procedures of health plans, healthcare providers, and Government health benefit programs.

Choosing an Insurance Plan There are a number of official government agencies that help consumers understand their healthcare insurance choices.53 The U.S. Department of Labor, in particular, recommends ten ways to make your health benefits choices work best for your family.54 1. Your options are important. There are many different types of health benefit plans. Find out which one your employer offers, then check out the plan, or plans, offered. Your employer's human resource office, the health plan administrator, or your union can provide information to help you match your family’s needs and preferences with the available plans. The more information you have, the better your healthcare decisions will be. 2. Reviewing the benefits available. Do the plans offered cover preventive care, well-baby care, vision or dental care? Are there deductibles? Answers to these questions can help determine the out-of-pocket expenses you may face. Cheapest may not always be best. Your goal is high quality health benefits.

More information about quality across programs is provided at the following AHRQ Web site: http://www.ahrq.gov/consumer/qntascii/qnthplan.htm. 54 Adapted from the Department of Labor: http://www.dol.gov/dol/pwba/public/pubs/health/top10-text.html. 53

Your Child’s Rights and Insurance 151

3. Look for quality. The quality of healthcare services varies, but quality can be measured. You should consider the quality of healthcare in deciding among the healthcare plans or options available to your family. Not all health plans, doctors, hospitals and other providers give the highest quality care. Fortunately, there is quality information you can use right now to help you compare your healthcare choices. Find out how you can measure quality. Consult the U.S. Department of Health and Human Services publication “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer. 4. Your plan's summary plan description (SPD) provides a wealth of information. Your health plan administrator can provide you with a copy of your plan’s SPD. It outlines your family’s benefits and your legal rights under the Employee Retirement Income Security Act (ERISA), the federal law that protects your family’s health benefits. It should contain information about the coverage of dependents, what services will require a co-pay, and the circumstances under which your employer can change or terminate a health benefits plan. Save the SPD and all other health plan brochures and documents, along with memos or correspondence from your employer relating to health benefits. 5. Assess your benefit coverage as your family status changes. Marriage, divorce, childbirth or adoption, and the death of a spouse are all life events that may signal a need to change your health benefits. You, your spouse and dependent children may be eligible for a special enrollment period under provisions of the Health Insurance Portability and Accountability Act (HIPAA). Even without life-changing events, the information provided by your employer should tell you how you can change benefits or switch plans, if more than one plan is offered. If your spouse's employer also offers a health benefits package, consider coordinating both plans for maximum coverage. 6. Changing jobs and other life events can affect your family’s health benefits. Under the Consolidated Omnibus Budget Reconciliation Act (COBRA), you, your covered spouse, and your dependent children may be eligible to purchase extended health coverage under your employer's plan if you lose your job, change employers, get divorced, or upon occurrence of certain other events. Coverage can range from 18 to 36 months depending on your situation. COBRA applies to most employers with 20 or more workers and requires your plan to notify you of your rights. Most plans require eligible individuals to make their COBRA election within 60 days of the plan's notice. Be sure to follow up with your plan sponsor if you don't receive notice, and make sure you respond within the allotted time.

152 Fragile X Syndrome

7. HIPAA can also help if you are changing jobs, particularly if you have a medical condition. HIPAA generally limits pre-existing condition exclusions to a maximum of 12 months (18 months for late enrollees). HIPAA also requires this maximum period to be reduced by the length of time you had prior “creditable coverage.” You should receive a certificate documenting your prior creditable coverage from your old plan when coverage ends. 8. Plan for retirement. Before you retire, find out what health benefits, if any, extend to you and your spouse during your retirement years. Consult with your employer's human resources office, your union, the plan administrator, and check your SPD. Make sure there is no conflicting information among these sources about the benefits your family will receive or the circumstances under which they can change or be eliminated. With this information in hand, you can make other important choices, like finding out if you are eligible for Medicare and Medigap insurance coverage. 9. Know how to file an appeal if a health benefits claim is denied. Understand how your plan handles grievances and where to make appeals of the plan's decisions. Keep records and copies of correspondence. Check your health benefits package and your SPD to determine who is responsible for handling problems with benefit claims. Contact PWBA for customer service assistance if you are unable to obtain a response to your complaint. 10. You can take steps to improve the quality of the healthcare and the health benefits your family receives. Look for and use things like Quality Reports and Accreditation Reports whenever you can. Quality reports may contain consumer ratings -- how satisfied consumers are with the doctors in their plan, for instance-- and clinical performance measures -- how well a healthcare organization prevents and treats illness. Accreditation reports provide information on how accredited organizations meet national standards, and often include clinical performance measures. Look for these quality measures whenever possible. Consult “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer.

Medicaid Illness strikes both rich and poor families. For low-income families, Medicaid is available to defer the costs of treatment. In the following pages, you will learn the basics about Medicaid as well as useful contact information on how to find more in-depth information.

Your Child’s Rights and Insurance 153

Medicaid is a joint federal and state program that helps pay medical costs for some people with low incomes and limited resources. Medicaid programs vary from state to state. You can find more information about Medicaid on the HCFA.gov Web site at http://www.hcfa.gov/medicaid/medicaid.htm.

NORD’s Medication Assistance Programs Finally, the National Organization for Rare Disorders, Inc. (NORD) administers medication programs sponsored by humanitarian-minded pharmaceutical and biotechnology companies to help uninsured or underinsured individuals secure life-saving or life-sustaining drugs.55 NORD programs ensure that certain vital drugs are available “to those families whose income is too high to qualify for Medicaid but too low to pay for their prescribed medications.” The program has standards for fairness, equity, and unbiased eligibility. It currently covers some 14 programs for nine pharmaceutical companies. NORD also offers early access programs for investigational new drugs (IND) under the approved “Treatment INDs” programs of the Food and Drug Administration (FDA). In these programs, a limited number of individuals can receive investigational drugs that have yet to be approved by the FDA. These programs are generally designed for rare medical conditions. For more information, visit www.rarediseases.org.

Additional Resources In addition to the references already listed in this chapter, you may need more information on health insurance, hospitals, or the healthcare system in general. The NIH has set up an excellent guidance Web site that addresses these and other issues. Topics include:56 ·

Health Insurance: http://www.nlm.nih.gov/medlineplus/healthinsurance.html

·

Health Statistics: http://www.nlm.nih.gov/medlineplus/healthstatistics.html

·

HMO and Managed Care: http://www.nlm.nih.gov/medlineplus/managedcare.html

·

Hospice Care: http://www.nlm.nih.gov/medlineplus/hospicecare.html

Adapted from NORD: http://www.rarediseases.org/cgibin/nord/progserv#patient?id=rPIzL9oD&mv_pc=30. 56 You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html. 55

154 Fragile X Syndrome

·

Medicaid: http://www.nlm.nih.gov/medlineplus/medicaid.html

·

Medicare: http://www.nlm.nih.gov/medlineplus/medicare.html

·

Nursing Homes and Long-term Care: http://www.nlm.nih.gov/medlineplus/nursinghomes.html

·

Patient's Rights, Confidentiality, Informed Consent, Ombudsman Programs, Privacy and Patient Issues: http://www.nlm.nih.gov/medlineplus/patientissues.html

·

Veteran's Health, Persian Gulf War, Gulf War Syndrome, Agent Orange: http://www.nlm.nih.gov/medlineplus/veteranshealth.html

Online Glossaries 155

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

·

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

·

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

·

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

·

On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/

·

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

·

Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html

Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a) and drkoop.com (http://www.drkoop.com/). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to fragile X syndrome and keep them on file. The NIH, in particular, suggests that parents of children with fragile X syndrome visit the following Web sites in the ADAM Medical Encyclopedia:

156 Fragile X Syndrome

·

Basic Guidelines for Fragile X Syndrome ADHD Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001551.htm Fragile X syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001668.htm Fragile X syndrome chromosome analysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003413.htm

·

Signs & Symptoms for Fragile X Syndrome Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm

·

Diagnostics and Tests for Fragile X Syndrome ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Chromosome analysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003935.htm Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm

·

Background Topics for Fragile X Syndrome

Online Glossaries 157

Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chromosome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002327.htm Genetic counseling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm Genetics Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Prenatal diagnosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Testes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002334.htm

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Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

·

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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FRAGILE X SYNDROME GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Aberrant: Wandering or deviating from the usual or normal course. [EU] Absenteeism: Chronic absence from work or other duty. [NIH] Accommodation: distances. [EU]

Adjustment, especially that of the eye for various

Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [NIH] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] Antidepressant: An agent that stimulates the mood of a depressed patient, including tricyclic antidepressants and monoamine oxidase inhibitors. [EU]

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Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Cerebellar: Pertaining to the cerebellum. [EU] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic examination. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body

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tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU] Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. [NIH] Dysplasia: Abnormality of development; in pathology, alteration in size, shape, and organization of adult cells. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: In animals, those derivatives of the fertilized ovum that eventually become the offspring, during their period of most rapid development, i.e., after the long axis appears until all major structures are represented. In man, the developing organism is an embryo from about two weeks after fertilization to the end of seventh or eighth week. [EU] Endogenous: Developing or originating within the organisms or arising

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from causes within the organism. [EU] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bedwetting, nocturnal enuresis). [EU] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other health-related event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Gaba: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility

Glossary 163

complex. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrocephalus: A condition marked by dilatation of the cerebral ventricles, most often occurring secondarily to obstruction of the cerebrospinal fluid pathways, and accompanied by an accumulation of cerebrospinal fluid within the skull; the fluid is usually under increased pressure, but occasionally may be normal or nearly so. It is typically characterized by enlargement of the head, prominence of the forehead, brain atrophy, mental deterioration, and convulsions; may be congenital or acquired; and may be of sudden onset (acute h.) or be slowly progressive (chronic or primary b.). [EU]

Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Hyperthyroidism: 1. excessive functional activity of the thyroid gland. 2. the abnormal condition resulting from hyperthyroidism marked by increased metabolic rate, enlargement of the thyroid gland, rapid heart rate, high blood pressure, and various secondary symptoms. [EU] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU]

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Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lithium: Lithium. An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH] Lobe: A more or less well-defined portion of any organ, especially of the brain, lungs, and glands. Lobes are demarcated by fissures, sulci, connective tissue, and by their shape. [EU] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an

Glossary 165

increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neurologic: Pertaining to neurology or to the nervous system. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Percutaneous:

Performed through the skin, as injection of radiopacque

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material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of YEASTS. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Reflux: A backward or return flow. [EU]

Glossary 167

Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Respiratory: Pertaining to respiration. [EU] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, hallucinations, emotional disharmony, and regressive behavior. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Stimulant: 1. producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. an agent or remedy that produces stimulation. [EU] Surgical: Of, pertaining to, or correctable by surgery. [EU] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU]

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Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a nonbarbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH]

Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Withdrawal: 1. a pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) a substancespecific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU]

General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna

·

Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational

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Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna ·

A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna

·

Dorland's Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna

·

Dorland's Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna

·

Dorland's Pocket Medical Dictionary (Dorland's Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618

·

Melloni's Illustrated Medical Dictionary (Melloni's Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna

·

Stedman's Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna

·

Stedman's Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna

·

Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna

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INDEX A Aberrant...........................................45, 47 Accommodation.............................24, 165 Adolescence ........35, 48, 53, 58, 159, 165 Alleles ..............35, 43, 46, 47, 49, 53, 163 Amantadine ...........................................14 Amniocentesis .................................13, 76 Antibody.................................................46 Anticonvulsant ...............................23, 160 Antidepressant...............................23, 162 Anxiety.......................................14, 17, 64 Arteries ..........................................80, 161 Assay...............................................50, 54 Atrophy ........................52, 78, 81, 99, 163 Atypical ..................................................64 Auditory ...................................54, 57, 122 B Bacteria .................................82, 128, 168 Biochemical ...............43, 51, 58, 121, 159 C Capsules..............................................131 Carbamazepine .....................................14 Carbohydrate.........................81, 130, 162 Cerebellar ..............................................52 Cerebral...............69, 78, 80, 81, 162, 163 Cherubism .............................................78 Cholesterol ..................................128, 130 Chromosomal ..............47, 65, 76, 79, 164 Chronic ............................69, 81, 147, 163 Cognition .........................................53, 86 Constriction............................................64 Cortical ....................................24, 78, 167 Cytogenetics..........................................75 Cytosine...........................................44, 47 D Degenerative .......................................129 Dextroamphetamine ..............................14 Diarrhea...............................................128 Dislocation .............................................26 Dysplasia .........................................78, 99 Dystrophy ..............................................70 E Electrophysiological.............................121 Embryo ......................23, 45, 82, 161, 165 Endogenous ..........................................50 Enuresis...............................121, 126, 162 Extracellular...........................................51 F Facial .........................................10, 19, 77 Fathers ..................................................64 Fibrosis ..................................................78

Fissure .................................................. 77 Fluorescence .......................... 50, 59, 162 Fluoxetine ............................................. 14 G Gastrointestinal ............................. 90, 162 Genotype ................................ 52, 59, 166 Glucose......................................... 80, 162 H Haplotypes ............................................ 53 Heredity................................................. 69 Hydrocephalus ...................................... 79 Hyperostosis ......................................... 78 Hypersensitivity............................. 14, 121 Hyperthyroidism ...................... 78, 81, 163 Hypertrophy .......................................... 78 Hypothyroidism ....................... 68, 81, 163 I Infantile ................................................. 78 L Lesion ......................................... 126, 164 Lithium .......................................... 23, 164 Lobe ...................................................... 16 Localization ......................................... 123 M Metaphase ............................................ 63 Methylphenidate ................................... 14 Midwifery............................................... 70 Mitosis................................................... 46 Molecular ... 17, 24, 42, 45, 47, 50, 55, 59, 62, 80, 92, 94, 96, 98, 161, 166, 168 Mosaicism ............................................. 63 Mucosa ........................................... 78, 82 Myopia .................................................. 16 N Neural ................................. 45, 55, 68, 69 Neurologic............................................. 26 Neurons .................................. 50, 60, 167 Neurotransmitter ............. 44, 59, 162, 165 Niacin .................................................. 129 O Osteogenesis .................................. 70, 78 Osteopetrosis........................................ 78 Otitis...................................................... 16 Overdose ............................................ 129 P Pediatrics .............................................. 84 Pemoline ............................................... 14 Phenotype................... 48, 51, 52, 59, 166 Potassium ........................................... 130 Predisposition ....................................... 79 Prenatal......................... 13, 19, 68, 69, 76

Index 171

Prevalence.................................41, 52, 62 Proteins .....47, 51, 65, 123, 128, 130, 163 Proximal.................................................47 Psychiatric .............................................69 Psychiatry ............................................166 Psychopathology .............................54, 74 Puberty ............................................14, 48 R Receptor ................................................53 Reflux ....................................................16 Regurgitation .........................................16 Respiratory ............................................78 Riboflavin.............................................128 S Schizophrenia..........................15, 35, 168 Seizures...... 14, 16, 23, 24, 41, 122, 160, 167 Selenium..............................................130

Serum ..................................... 68, 82, 167 Skeletal ................................................. 40 Species ....... 58, 59, 74, 82, 161, 164, 167 Stimulant ................. 23, 24, 161, 164, 165 Surgical ..................... 33, 79, 84, 162, 165 Synaptic ............................ 49, 54, 59, 165 T Temperament ....................................... 48 Thalidomide .......................................... 79 Thermoregulation................................ 128 Thyroxine ............................................ 130 Transgenes ........................................... 54 Translating ............................................ 50 Tremor ............................................ 52, 99 Tricyclic ................................... 14, 22, 159 W Withdrawal ............................................ 26

172 Fragile X Syndrome

Index 173

174 Fragile X Syndrome