CONTENTS
FOREWORD TO THE THIRD EDITION
FOREWORD TO THE SECOND EDITION
FOREWORD TO THE FIRST EDITION
PREFACE
CONTRIBUTORS
1 Introduction
THE ORGANIZATION OF THIS BOOK
CATEGORIZATION OF DISORDERS
MEASUREMENTS
COMMON GENETIC TERMINOLOGY
PATTERNS OF INHERITANCE
GENETIC TESTING
ROLE OF THE MEDICAL GENETICIST AND GENETIC COUNSELOR
ADDITIONAL RESOURCES AND WEB SITES
2 Aarskog Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
3 Achondroplasia
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
4 Alagille Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
5 Albinism: Ocular and Oculocutaneous Albinism and Hermansky-Pudlak Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
6 Angelman Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
ACKNOWLEDGMENTS
REFERENCES
7 Arthrogryposis
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
OTHER RESOURCES
REFERENCES
8 ATR-X: α-Thalassemia Mental Retardation-X-Linked
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
9 Bardet-Biedl Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
10 Beckwith-Wiedemann Syndrome and Hemihyperplasia
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
11 Cardio-Facio-Cutaneous Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
12 CHARGE Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
13 Coffin-Lowry Syndrome
INTRODUCTION
DIFFERENTIAL DIAGNOSIS
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
14 Cohen Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
15 Cornelia de Lange Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
16 Costello Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
17 Craniosynostosis Syndromes
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
18 Deletion 1p36 Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
19 Deletion 4p:Wolf-Hirschhorn Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
20 Deletion 22q11.2 (Velo-Cardio-Facial Syndrome/DiGeorge Syndrome)
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
21 Deletion 22q13 Syndrome: Phelan-McDermid Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
22 Denys-Drash and Frasier Syndromes
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
23 Down Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
24 Ehlers-Danlos Syndromes
INTRODUCTION
THE CLASSIC TYPE
THE HYPERMOBILITY TYPE
THE VASCULAR TYPE
THE KYPHOSCOLIOSIS TYPE
THE ARTHROCHALASIA TYPE
THE DERMATOSPARAXIS TYPE
OTHER EHLERS-DANLOS SYNDROME VARIANTS
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
25 Fetal Alcohol Syndrome and Fetal Alcohol Spectrum Disorder
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
26 Fetal Anticonvulsant Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
27 Fragile X Syndrome and Premutation-Associated Disorders
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
28 Gorlin Syndrome: Nevoid Basal Cell Carcinoma Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
29 Hereditary Hemorrhagic Telangiectasia
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
30 Holoprosencephaly
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
31 Incontinentia Pigmenti
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
32 Kabuki Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
33 Klinefelter Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
OTHER MALE X CHROMOSOME ANEUPLOIDY
RESOURCES
REFERENCES
34 Marfan Syndrome
INTRODUCTION
ETIOLOGY, PATHOGENESIS, AND GENETICS
MANIFESTATIONS AND MANAGEMENT
DEVELOPMENT AND BEHAVIOR
RESOURCES
REFERENCES
35 Mowat-Wilson Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
36 Myotonic Dystrophy Type 1
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
37 Neurofibromatosis Type 1
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
38 Noonan Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
39 Oculo-Auriculo-Vertebral Spectrum
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
40 Osteogenesis Imperfecta
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
41 Pallister-Hall Syndrome and Greig Cephalopolysyndactyly Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
42 Prader-Willi Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
43 Proteus Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
44 PTEN Hamartoma Tumor Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
45 Rett Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
46 Robin Sequence
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
47 Rubinstein-Taybi Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
48 Russell-Silver Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
49 Smith-Lemli-Opitz Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
50 Smith-Magenis Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
51 Sotos Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
52 Stickler Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENTS
RESOURCES
REFERENCES
53 Treacher Collins Syndrome and Related Disorders
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
54 Trisomy 18 and Trisomy 13 Syndromes
INTRODUCTION
TRISOMY 18
INTRODUCTION
TRISOMY 13
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
55 Tuberous Sclerosis Complex
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
56 Turner Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
57 Vater/Vacterl Association
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
RESOURCES
REFERENCES
58 von Hippel-Lindau Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENT
RESOURCES
REFERENCES
59 WAGR Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENT
RESOURCES
REFERENCES
60 Williams Syndrome
INTRODUCTION
MANIFESTATIONS AND MANAGEMENT
ACKNOWLEDGMENT
RESOURCES
REFERENCES
Index
Copyright © 2010 by John Wiley & Sons, Inc. All rights reserved
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Library of Congress Cataloging-in-Publication Data:
Management of genetic syndromes / [edited by] Suzanne B. Cassidy, Judith E.
Allanson. – 3rd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-470-19141-5 (cloth)
1. Genetic disorders. I. Cassidy, Suzanne B. II. Allanson, Judith E.
[DNLM: 1. Genetic Diseases, Inborn–diagnosis. 2. Abnormalities, Multiple–diagnosis. 3. Abnormalities, Multiple–therapy. 4. Genetic Diseases, Inborn–therapy. QZ 50 M2655 2010]
RB155.5.M36 2010
616’.042–dc22
2009031379
We dedicate this book to our families:
Helene and Maurice Bletterman (deceased)
Joshua Cassidy
Francine Noftle
Jack and Barbara Robinson
Christopher Visher
For all they taught us, for their tolerance, and for all their love and encouragement.
FOREWORD TO THE THIRD EDITION
Cassidy and Allanson have done it again: produced a new edition of the one must-have book on management of genetic disorders for health care providers of all specialties. To incorporate advances in medical genetics into their practices, clinicians need an expert-authored resource that provides up-to-date information on available diagnostic approaches and practical day-to-day, age-oriented management. Management of Genetic Syndromes does not require that clinicians become genetics experts or fluent in genetics lingo. It is written with the knowledge that persons with inherited disorders are found in all medical practices and, similar to people with other medical conditions, these individuals will benefit most when their health care providers are comfortable with the issues that need to be addressed to assure the best medical and quality-of-life outcomes. This book presents to clinicians in primary care and specialty practice the infor-mation necessary to allow the clinician to decide for their patients with rare inherited disorders which care is within the scope of his or her practice and which specific needs should be referred out to other specialists.
Management of Genetic Syndromes is a boon to busy primary care practitioners who, I am told, have 90 seconds in which to answer a question brought up during a patient visit. If clinicians do not have a reliable, easy-to-use resource, those questions will go unanswered. The logical division of chapters by disorder and the thoughtful and consistent layout of each chapter into sections on diagnosis first (how can you provide disorder-specific care if you can’t be sure that you have the correct diagnosis?) followed by detailed management issues by organ system for all ages allows the busy clinician to hone in on an authoritative answer in a predictable “place.” Eliminating the guess work about specific care issues is tremendously valuable to busy clinicians who want to assure the best care for their patients, but cannot take the time to second guess the exact needs for an individual with a one-of-a-kind disorder in their practice. Similar to all quality information resources, Management of Genetic Syndromes provides citations to more detailed documentation of diagnostic and management recommendations for those clinicians with the time or inclination to learn more.
In these days of hype on pending cutting-edge treatment for genetic disorders and “personalized” medicine, clinicians need a filter that can separate what is really known about treatment and what is hypothesis-driven wishful thinking for which no prescription can be written. Management of Genetic Syndromes provides this filter, thus assuring clinicians and families that clinicians have at their fingertips information that will be most useful.
Although the promise of the Human Genome Project to provide gene-based therapy for inherited disorders is still a long way from reality, other aspects of the discoveries of the molecular basis of inherited disorders have benefited those with and at risk for inherited disorders. One example is surveillance of those at risk for a potential complication of an inherited disorder, which enables early diagnosis and, hence treatment to improve outcome. For example, in families with an inherited cancer predisposition, such as a hereditary colon cancer syndrome, at-risk relatives benefit from knowing who has inherited the family-specific mutation and who has not, so that those at greatest risk are screened using disease-specific protocols starting at the appropriate age and those who are not at increased risk are advised to follow population-based screening protocols. Management of Genetic Syndromes emphasizes the practical approach to the risk-defining use of molecular genetic testing with outcome-oriented surveillance. The reader does not need to be familiar with the jargon or principles of molecular genetics to understand how to use this approach for the benefit of patients in his or her practice.
Those with genetic disorders and their families often appreciate transparency in the care that they receive and they want access to the same information as their health care providers. The workman-like, practical approach to management in this book provides a “checklist-like” view that enables clinician and patient to follow together the issues to be addressed and their timelines. The chapters in Management of Genetic Syndromes are excellent “handouts” at clinic visits. In my academic clinical practice of medical genetics, my colleagues and I have on hand a ready supply of copies of the chapters of Management of Genetic Syndromes, which we read before the clinic visit and then provide to families at the time of their clinic appointment and to the referring clinicians with the clinic note. We know that, although the primary audience for this book is not affected individuals and their families, and, therefore, it was not written at the appropriate level for this audience, the clear, no-nonsense presentation style makes the content accessible to those families seeking to partner with their physician in their care.
Increasingly, families play a key role in the management of their inherited disorder, which most commonly is a chronic lifelong condition that may affect other family members of all generations. Consumer-oriented health information sources have grown exponentially with the discovery of the molecular genetic basis of inherited disorders, the growing use of the Internet, and the development of hundreds of disease-oriented patient advocate groups. Consumer health information resources, which often provide the most practical day-to-day information available for patients and their families, are a valuable adjunct to clinic visits. The essential role of consumer health information is acknowledged by Management of Genetic Syndromes by providing information on these resources in an easy-to-find location at the end of each chapter.
Management of Genetic Syndromes is an unparalleled medical genetics information resource for students, be they medical students, residents in primary care fields or specialty fields, or participants in continuing medical education. It is the one book I tell them to buy.
When I see the Management of Genetic Syndromes in a clinician’s office, I respect that clinician for taking the initiative to anticipate the needs of his or her patients with rare inherited disorders and know that the clinician, his or her patient, and the patient’s family will be grateful for the practical approach of this trusted colleague on the bookshelf.
ROBERTA A. PAGON, MD
University of Washington and Seattle
Children’s Hospital
FOREWORD TO THE SECOND EDITION
It was not very many years ago that the coupling of the terms “management” and “genetic syndromes” would have been regarded as an oxymoron. With the exception of the inborn errors of metabolism, the notion of managing genetic disorders would have been considered quite foreign and of managing genetic syndromes, by which we mean conditions in which several organ systems and/or parts of the body are affected, even more so. The principal role of the medical geneticist was to diagnose these conditions as best as he or she could. Management, such as it was, was essentially symptomatic and was usually left to primary care physicians and medical specialists with little direct knowledge of the syndromes themselves. The literature on genetic syndromes reflected this situation. It was, for the most part, descriptive, and the emphasis was on diagnosis. Although many admirable reference books on diagnosis were written, most notable of which was (and still is), Smith's Recognizable Patterns of Human Malformations, it was frequently difficult to find definitive information about how to manage these conditions once the diagnoses had been made.
However, much has changed recently with regard to genetic syndromes, with perhaps the most important change being societal, not medical or scientific. It is now generally accepted that persons with genetic syndromes, whether associated with mental retardation or not, should, if possible, be treated. This was not always so, and a graphic example of how thinking has altered is provided by Down syndrome, certainly one of the quintessential genetic syndromes. Within my professional lifetime, there has been a shift from exclusion from society, generally by institutionalization, to rearing at home, educational inclusion, and participation in all aspects of daily life. Similarly, a policy of nonintervention, often with certain death, when major heart or gastrointestinal abnormalities were present has been replaced by aggressive surgical correction. Guidelines for the prevention of known complications have been developed, and their implementation is now commonplace. As a result, these changes have led, even without any specific therapy for Down syndrome, to an increase in lifespan, better cognitive development, and an overall improvement in the quality of life, both physically and socially.
In addition to the attitudinal shift, there have been many medical and scientific advances that have altered our approach to genetic syndromes. The mutations that cause many of the monogenic or contiguous gene syndromes are now known, and more are being discovered almost daily. The functions of the genes that these mutations affect are gradually being elucidated. For the aneuploidies, the mapping of the human genome is providing information about how many and which genes are at dosage imbalance. All of this has changed genetic syndromes from being curiosities that could not be understood to disorders that can be rationally approached in terms of cause and potential therapy, another and quite major change in attitude. This information has also led to the development of molecularly based tests that are greatly improving disease diagnosis and are permitting discrimination among conditions that had hitherto been confused with one another. In the future, this genetic information promises to lead to therapies that are tailored to individual diseases. In addition, medical diagnostic procedures and therapeutic approaches have become much more powerful. These include, for example, the various forms of imaging, surgical techniques such as for complex congenital heart defects or ambiguous genitalia, and highly specific and potent pharmacological agents. And, finally, more is continually being learned about the long-term consequences of genetic syndromes—about their natural histories—which is essential if comprehensive approaches to management are to be developed.
So, if societal attitudes have changed and genetic and medical information and capabilities are rapidly expanding, who should be undertaking the management of persons with genetic syndromes? Who should be reading this book? There is no simple answer to this question, because in a sense each syndrome must be dealt with on its own merits. Given the multitude of systems that these syndromes may affect and the different combinations of abnormalities that may occur in one compared with another, the approach to management needs to be quite flexible. Nevertheless, someone must be responsible for the overall coordination of care. Who this will be will depend on local circumstances, but the important thing is that it be someone who is knowledgeable and willing to act in the interests of the affected individual.
In most instances, persons with genetic syndromes are usually managed by a mix of genetic professionals, primary care physicians, and medical and other specialists. By “genetic professional” I mean medical geneticists, genetic counselors and genetic nurses, and laboratory geneticists who have special knowledge about and experience in deal-ing with a large number of genetic syndromes that are individually quite uncommon or rare. For the most part, genetic professionals have traditionally been engaged in the diagnosis and counseling of these conditions. Unlike the situation with inherited metabolic disorders, in which geneticists do participate directly in therapy, their involvement in the therapeutic aspects of the management of genetic syndromes has generally involved referrals to appropriate specialists for specific forms of medical or surgical therapy. Primary care physicians, in addition to providing day-to-day care of individuals with genetic syndromes, often act as intermediaries in the referral process. And, beyond this list of medical personnel, a variety of other professionals and social and educational organizations, both governmental and voluntary, also provide many services to affected individuals and their families.
In some instances, the medical specialists, genetic profes-sionals, and allied health professionals work together in multidisciplinary clinics devoted to individual disorders (e. g., Marfan or Down syndrome) or groups of related disorders (craniofacial anomalies or skeletal dysplasias) or perhaps even to birth defects more generally. These clinics provide a coordinated approach to management that is usually more efficient from the point of view of providers and of affected individuals and their families than is possible when many independent providers are involved in the care of the patient and may be a model for the provision of services in the future.
Regardless of how the services are organized and of who is actually coordinating management, many providers with different degrees of knowledge about any particular condition are likely to be involved. It is, therefore, essential that each understand what he or she is dealing with and what will be required to properly care for the affected individual and his or her family, and it is here that this volume, Management of Genetic Syndromes, uniquely fills a void that has long existed in the literature on genetic syndromes. Gathered together within a reasonably compact volume are authoritative descriptions written for a diverse readership of the management of over 50 of the most common conditions that fall within the rubric of genetic syndromes (including two that are primarily teratogenic, but are usually grouped with the others). The concept of what is entailed in management is broadly interpreted. Therefore, each chapter begins with considerations of etiology, pathogenesis, genetics, and diagnosis (including diagnostic criteria, testing, and differential diagnosis), all of which are necessary if the patient and his or her condition are to be fully understood. These are then followed by detailed discussions of what might be considered to be at the heart of management—the evaluation of each of the relevant systems and the treatment of the abnormalities that are likely to be present. The chapter concludes with selected references and a listing of available support groups and other resources. The evaluation and treatment sections are greatly enhanced by the use of an outline form of presentation, with bullets to highlight individual points.
When it appeared in 2001, the first edition of this book was eagerly seized upon by the medical genetics community. The need was there, and there was nothing else like it. From my own personal experience and observation in a genetics service that handles a large number of persons with genetic syndromes, I can testify that the book rapidly proved to be of great value to all of the clinic personnel—geneticists and counselors, physicians and nonphysicians, students, residents, and fellows. The rapid appearance of this second edition indicates that my own experience has been more generally shared, and the near doubling of the number of conditions covered will make the book even more valuable than before. Given the rapid progress that is being made in genetics and medicine and in the ability to diagnose and treat genetic syndromes, it is likely that frequent revisions will be required.
CHARLES J. EPSTEIN
Department of Pediatrics
University of California,
San Francisco
FOREWORD TO THE FIRST EDITION
This is a book whose time has come. Genetic disorders and syndromes are usually though of as being rare, and yet for affected individuals, their families, and their primary and specialty care physicians, it is essential to have reliable information about the natural history and management of the specific disorders.
The thirty conditions described in this book may seem rare (with incidences between 1 in 600 and 1 in 60,000). However, when you put together all the individual cases or a particular condition in North America, in Europe, and in the world, a very large number of affected individual will benefit from the information in this book. In the past it has been difficult to bring together information of this type about specific disorders, and that is why this book fills a very important niche. It becomes a model for how to organize information that is needed for the families and primary care providers to manage the many, many other genetic disorders, congenital anomalies, and syndromes that are known to occur. The book is written in understandable language appropriate for families and for primary care and specialty physicians. It is major contribution.
Over the last two decades, remarkable progress has been made with regard to developing diagnostic tests and unraveling the human genome. Within the next few years all of the human genes will have been defined. The next major goal in genetics will be to understand how genes interact and function, both in the course of development and over a lifetime. In addition to the remarkable progress in basic and clinical genetics, there has been increasing communication and access to information. Through the Internet, the public has access to research reports and data that were usually not readily available in the past. However, it is essential to put that information into a meaningful form and context. That is exactly what this book does. The communication explosion has allowed the networking of researchers and families. The development of parent/lay support groups has led to a cooperation between researchers and families that has helped to define the natural history and the variation that can be seen in a specific disorder.
What every family and physician wants is to provide the best care possible for the affected individual. Nobody wants to miss the opportunity for that individual to reach his or her full potential, to benefit from a useful therapy, or to avoid a complication. Parents need an understanding of what will happen over time so that they can plan. They don't want to waste money and effort going from expert to expert or doing test after test. They need a realistic approach to what they should expect both in childhood and adulthood. They also usually want to know whether there is some risk of recurrence of the condition in their other children, in other family members, and in the affected individual's offspring. They want to know whether prenatal diagnosis is available, and they want to know the spectrum of variation that can occur. The beauty of this new bookisthatitprovides that kind of information for each specific disorder in a logical and understandable form. Most families and physicians will focus in on the chapter relevant to a specific individual. However, they can't help but glance at other chapters and see the remarkable spectrum of complications that are not present in the disorder of interest to them. They are likely to benefit from this broader perspective.
Most pediatricians will have heard of all thirty disorders; however, some primary care and specialty physicians may not have heard of a specific disorder until they have the affected individual in their practice. The book should help to alert health care professionals to consider these conditions and should lead to appropriate testing to make a correct diagnosis, reducing the time it takes to make a specific diagnosis. Two-thirds of the conditions in this book have a specific diagnostic test, but the other one-third require “pattern recognition” and an alert, trained health care professional to consider the diagnosis.
It can be expected that additional advances will be made over the next few decades leading to better understanding and better management. So this book is already dated! There is still a lot to be learned! In fact, every family and every affected individual will contribute to that increased knowledge by giving feedback to the authors. Disorder-specific parent/lay support groups will continue to play in important role in improving our understanding. The authors of each chapter have worked together with the support groups and are very aware that it is the process of working together with these groups and the members' willingness to provide information that has led to present-day understanding. We are all very grateful to each of the parents and affected individuals who have taken part in studies that have advanced our knowledge.
To write a book about management, it is necessary to know the natural history of the disorder. The authors of each of these chapters have a wealth of experience and knowledge that has been collected over the least couple of decades. Understanding the natural history not only tells us what to expect at various ages but also how to recognize various complications. It is important to understand the natural history of the condition to determine whether various therapies actually improve the outcome. It is important to understand the natural history to recognize subgroups representing the variability and heterogeneity within the disorder. It is important to understand the natural history to learn the mechanisms that lead to the disorder, e.g., what sort of gene is likely to be involved? Where is the mutation in the gene? How does that mutation relate to severity of complications? How big is the deletion? Does that size relate to severity of complications? How does this gene act against the background of other genes or pathways? Is it possible to recognize a cellular mechanism leading to this disorder? Are there parent-of-origin effects on the expression of the gene or the mutation rate? Are there hot spots that have markedly increased mutation rates? Does the place on the chromosome where the gene lies put it at increased risk for mutation? These are only a few of the questions we hope to answer over the next few decades.
No one is more motivated than the family or the affected individual to learn about these disorders. It is important for them to be as knowledgeable as possible. The families of an affected person usually know more about the condition than most of the physicians they visit. It is important for families to continue to ask questions and to gain as much knowledge as possible to ensure the best outcome for the affected individual. It is important for families and affected individuals to keep their own records about the affected individual, such as a notebook of their visits to health care facilities, copies of the reports, and the resultsofthe tests that havebeen done.Itis also important to keep a photographic record of changes over time.
Once a family or an affected individual becomes involved in collecting information about the disorder, they often develop quite creative ideas that challenge the standard way of thinking about the disorder. Part of the advantage of participating in a support group is that those ideas then can be shared with the medical advisors and researchers and may lead to new knowledge.
Much of ourunderstanding of these disorders is based on the manifestations in childhood, on feeding, on growth and development, and on social skills. However, information on adults is also beginning to accumulate and has been included in this book. In some conditions there is a stable situation, in others there is improvement with aging, and in still others deterioration can be expected. For many of the conditions described in this book, behavioral patterns have been recognized.
How should a family and their primary car physician use the experts? It would be impossible for the authors of these chapters to see every individual with the condition, but it is usually helpful for a family and the affected individual to see a clinical geneticist, to visit a developmental center, or to use the multidisciplinary team that is available in their area. Over the years, specialty clinics to deal with specific conditions have been developed. At some time it is probably appropriate to visit such a clinic at least once to review the affected individual's progress and to consider any special complications or responses. On the other hand, it is very important to have a knowledgeable primary care physician who cares for day-to-day medical needs and is aware of the unique complications of the condition.
The parent/lay support groups form an international network keeping up with new information on the specific disorders, and new information is sure to come. Some new information will come through organized studies of natural history; other data will come through clinical trails of new therapies; and further information will come from basic work on cellular mechanisms and biochemical pathways. For many of these disorders animal models will be developed, such as mice with the specific disorder, so that various therapies can be considered before trails in human beings. We live in a very exciting age and can anticipate major advances over the next few decades for each of the disorders described in this book. The international network of families, affected individuals, and researchers should and will communicate about new ideas, innovative approaches, and better understanding about these conditions.
We have begun to enter an era of evidence-based medicine. Only by having natural history information is it possible to understand the benefits of new interventions and therapies. We will hope that this book is outdated very rapidly because of such new developments, but in the meanwhile this book on management of common genetic syndromes is extremely welcome to families and health care providers alike.
JUDITH G. HALL
Professor and Head, Department of Pediatrics
University of British Columbia and
British Columbia Children's Hospital
Professor, Medical Genetics
James and Annabelle McCreary Professor
University of British Columbia
PREFACE
This book is designed to assist primary care physicians, medical specialists, other care providers, and families in assuring optimal care for individuals who have multiple problems that are components of genetic syndromes. It represents the combined experience and knowledge of many experts in medical genetics and related fields, each of whom has spent years participating in the diagnosis and clinical management of a specific genetic syndrome. Most of the chapter authors have conducted major clinical research on “their” respective disorders.
The syndromes selected for inclusion in this book are those that are sufficiently common as to be regularly encountered in clinics specializing in genetics, development, neurology, or craniofacial disorders. Many of these disorders would not have been seen in the practice of most primary care physicians or non-genetics specialists. When they are encountered, the physician typically has little knowledge of how to confirm the diagnosis, identify the associated problems and clinical manifestations, and optimally care for the affected individual. This lack of knowledge is due only partly to infrequent exposure to the disorder. For many of these conditions, very little concerning management has been published, and a search for this knowledge is extremely time-consuming, often provides incomplete information, and is frequently futile. This book was designed to provide that knowledge, based on the cumulative experience of an expert or experts on each condition. As a result, a significant proportion of the information found in this source will be personal experience or observation. In most cases, there is no established “standard of care” based on controlled trials or outcome studies. Nonetheless, the editors have sought to provide the reader with information that is as reliable as possible. Where available, reference to evidence-based studies and other published sources has been included: where unavailable, reference to the author(s)’ “personal experience” or “personal observation” has been noted, to reflect non-peer-reviewed information.
Deciding on which disorders to include is no mean task, and there are some disorders for which there is little accu-mulated experience in management. There are several disorders that are included in this third edition that were not in the first two editions. Others will be included in future editions as new experience accumulates. In addition to more than 50 genetic (or probably genetic) conditions, two terato- genic disorders, fetal alcohol syndrome and fetal anticonvulsant syndrome, are also included because of their frequency and because genetic factors influence susceptibility.
The editors hope that this continues to be a useful text to primary care physicians, medical geneticists, and other medical specialists, educators, and other providers of care for the individuals and families affected with these common genetic syndromes. Similar to those with more frequent medical conditions, they deserve the best possible medical, educational, and psychological care.
We are appreciative of the two editors from Wiley-Liss, Collette Bean for giving us the opportunity to compile this book, and Thomas Moore for his assistance in editing. Most importantly, we thank the contributors and the many patients for their willingness to have their photographs published in this book and for their participation in the clinical research that provided the information for its content.
SUZANNE B. CASSIDY
JUDITH E. ALLANSON