Management of Prader-Willi Syndrome

Management of

Prader-Willi Syndrome

Third Edition

La Monstrua vestida La Monstrua desnuda

These paintings by the Spanish baroque court painter Juan Carreño de Miranda (1616-1685)

depict Doña Eugenia Martinez Vallejo at approximately 6 years of age (c. 1680), after she was

brought to the court of Charles II of Spain and given the moniker “La Monstrua.” It is said

that upon viewing these paintings in the Museo del Prado, Madrid, Dr. Andrea Prader immedi-

ately recognized features consistent with Prader-Willi syndrome. Although we may never

know if this child did in fact have PWS, the paintings and contemporaneous 17th century

descriptions of her condition strongly support this supposition. Indeed, these paintings are

often regarded as the earliest illustrations of PWS. La Monstrua has continued to be an

intriguing fi gure, as evidenced by an outdoor sculpture in Avilés created in 1997 by the

Spanish artist Amado González Hevia “Favila” (b. 1954; www.amadofavila.com) based on

these baroque portraits.

Management of

Prader-Willi Syndrome

Third Edition

Merlin G. Butler, MD, PhD

Chief, Section of Medical Genetics and Molecular Medicine, William R.

Brown/Missouri Chair of Medical Genetics and Molecular Medicine;

Professor of Pediatrics, University of Missouri-Kansas City School of Medicine, Children’s Mercy Hospitals and Clinics, Kansas City, Missouri

Phillip D.K. Lee, MD

Chief Scientifi c Offi cer, Immunodiagnostic Systems Ltd., Boldon, Tyne and Wear, United Kingdom

Barbara Y. Whitman, PhD

Professor of Pediatrics, Saint Louis University School of Medicine, Cardinal Glennon Children’s Hospital, St. Louis, Missouri

Editors

With 125 Illustrations, 11 in Full Color

Merlin G. Butler, MD, PhD Phillip D.K. Lee, MD Chief, Section of Medical Genetics Chief Scientifi c Offi cer

and Molecular Medicine Immunodiagnostic Systems Ltd.

William R. Brown/Missouri Boldon, Tyne and Wear Chair of Medical Genetics and NE 35 9PD

Molecular Medicine UK

and

Professor of Pediatrics Barbara Y. Whitman, PhD University of Missouri-Kansas Professor of Pediatrics City School of Medicine Saint Louis University School Children’s Mercy Hospitals of Medicine

and Clinics Cardinal Glennon Children’s Hospital Kansas City, MO 64108 St. Louis, MO 63104

USA USA

Supported by an unrestricted grant from Pharmacia Corporation, a division of Pfi zer, Inc.

Library of Congress Control Number: 2005930806

ISBN 10: 0-387-25397-1 ISBN 13: 978-0387-25397-8 Printed on acid-free paper.

© 2006, 1995 by the Prader-Willi Syndrome Association (USA)

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, Inc., 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar meth- odology now known or hereafter developed is forbidden.

The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identifi ed as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.

While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed in the United States of America. (BS/MVY) 9 8 7 6 5 4 3 2 1

springeronline.com

Foreword I

In 1988, when the fi rst edition of Management of Prader-Willi Syndrome was published, my daughter turned eight years old. That year, due to advances in chromosomal analysis, Gabriella was diagnosed with Prader-Willi syndrome (PWS). After searching for answers so long, we were relieved to fi nally have a name attached to the challenges we faced. At that time, we were especially grateful for this handbook and for the tools it provided to assist us in confronting the daily manage- ment of this disorder. However, reading the prognosis for Gabriella’s (and our family’s) future was disheartening. Although we remained determined to provide her with the best possible opportunities for living her life to the fullest, it was diffi cult to see even a glimmer of sunshine.

During the past two decades, I have watched this small spark of light grow into an expanding ray of hope. There have been countless advances in the diagnosis and management of PWS, and many of our children have reaped the benefi ts of these new possibilities. With the advent of the Internet, the world of PWS expanded, families connected, and awareness of the syndrome was suddenly available to anyone who had access to a computer. Early diagnosis, early education, and timely treatment provide the key to a better quality of life for people with PWS. In many countries, several options for treatment are available; in other nations, it is still impossible to receive a diagnosis or even get necessary medical services. The International Prader-Willi Syndrome Organization (IPWSO) provides education, and it encourages nations to share their knowledge and resources in order to narrow this dispar- ity of services. The third edition of Management of Prader-Willi Syndrome is a fi ne example of collaboration, which will benefi t patients through- out the world.

Now we are at the cusp of innovative and extraordinary scientifi c discoveries. As this book becomes a reference around the world, it is our hope that this comprehensive resource of expertise will provide the impetus and inspiration for even more exploration and answers to the complexity of this disorder.

v

On behalf of our global family, the IPWSO, I wish to express our heartfelt thanks to the editors, authors, and others who graciously put so many hours into making this book possible. This edition is excep- tional because it represents direct and indirect contributions from a network of professionals and parents from across continents. Their combined efforts will be heard around the world and will make a dif- ference to so many families in so many signifi cant and extraordinary ways. Families no longer need to feel isolated, and with knowledge in hand, they can better face the challenges of PWS. This management book provides tangible assistance and represents hope for the future, turning the dream of a better life for people with PWS into a reality.

Pamela F. Eisen President, International Prader-Willi Syndrome Organization

(IPWSO)

vi ^{Foreword I}

Foreword II

It seems yesterday to me, but it was 27 years ago when I was told that my son Daniele had Prader-Willi syndrome. I felt lost and confused then, because the little information I found available in Italy was not encouraging at all; I could not believe my lovely son was going to die soon, as the literature said. Inside Daniele’s eyes I saw his joy of being part of this world. He was ready and willing to face and share, because he had, as he proved, a lot to give. My wife and I decided to do every- thing we could not to accept the tragic fate it seemed we had to face.

Today I must thank my son’s eyes for giving me such an inspiration to struggle and keep struggling as President of the International Prader-Willi Syndrome Organization (IPWSO). I am proud to have represented an organization whose now 60 member countries tire- lessly work through their qualifi ed and enthusiastic professional and parent delegates. This close cooperation between parents and profes- sionals, with active participation and sharing information together, makes our organization a unique example in the world. It is clear that the results we have achieved are extremely important, giving all involved families hope and positive references for the future of their children.

The rapid expanding of our contacts worldwide through the Internet puts us in contact every day with affected families from different coun- tries, cultures, and realities. It is incredible how desperate mothers become inspired, how discouraged presidents or delegates of local associations become both inspired and effi cient, and how doctors become important sources of information for their colleagues previ- ously unknown to them, share scientifi c information, and cooperate in research worldwide after an active e-mail exchange. There is still a lot to do. We estimate that many, perhaps most, of the affected individuals worldwide are unknown; too many affected people sadly die before we are able to locate them and provide support. Member countries of IPWSO are designated on a world map with a fl ag. Large areas such as in Eastern Europe, Africa, and Asia are still without a fl ag; we keep working hard to spread our voice. In some countries, as recently hap- pened with China, the scientifi c contacts with doctors participating in

vii

international scientifi c meetings or studying abroad are the right channel to follow for opening heavy or hidden gates.

This third edition of Management of Prader-Willi Syndrome is yet another excellent tool for soundly informing professionals about the syndrome, especially in countries that lack information or where no parent organization yet exists. It is an example of the steady and hard work of people from multiple disciplines dedicated to study and research on PWS throughout the world. I am proud and honored to write a few words as introduction to this book, hoping its distribution will cover all continents and reach as many professionals as possible.

On behalf of the IPWSO Board, I wish to thank all authors for their precious contribution to making this third edition an important mile- stone in our mission to know more about the syndrome that affects special children of special parents, and who are followed by special doctors.

Giorgio Fornasier Past President, Director of Program Development, International

Prader-Willi Syndrome Organization (IPWSO)

viii Foreword II

Preface

ix In the fi rst edition of Management of Prader-Willi Syndrome, published

in 1988, Dr. Hans Zellweger wrote in the foreword, “I . . . have reached the conclusion that PWS is one of the two most grave ailments I have encountered. . . . “Fortunately, if Hans were still alive, I think he would fi nd that this is no longer the case. Although still complex to manage and challenging at times, the world of Prader-Willi syndrome today is much more hopeful. Our son, Matt, was a teenager at the time Dr.

Zellweger wrote that “Family systems deteriorate and life becomes hell for all concerned.” Although we did cringe at those words at the time, I can now smile and breathe a sigh of relief to know that we, and many other parents, have delightful young adult children who are a joy to know.

Rereading the 1988 foreword made me appreciate just how far we have come. Many of our children are now diagnosed as newborns thanks to increased awareness and the availability of accurate, confi r- matory genetic testing. Parents are now educated about the syndrome much earlier and in far greater depth; as a result they are now far more sophisticated advocates for their children with physicians, schools, and other care providers. Parents insist on, and frequently provide, more comprehensive education of professionals. Early identifi cation and strong advocacy, combined with in-depth research has resulted in many of our children now being tall (thanks to growth hormone), slim (thanks to early intervention and good environmental controls), and happy (thanks to good behavior management and psychotropic medi- cation). This is a new generation of children with many options for treatment and management.

This third edition of Management of Prader-Willi Syndrome is crucial

because the world is bursting with new alternatives for diagnosis and

treatment, but that information typically gets to professionals in bits

and pieces. In this book, the editors present the current understanding

of cause and diagnosis and pull together a comprehensive approach to

treatment from the wisdom of many renowned experts in the fi eld of

PWS.

With the Internet, we also now have an entire world of expert knowl- edge to pull from—and an entire world of PWS for which we are responsible. At the PWSA (USA) offi ce, pleas for help do not just come from states like Kentucky, California, and Texas anymore. They also come from countries such as India, Romania, Tanzania, and Brazil. As we reach across continents with the stroke of a key, our goal is that this book also is far-reaching, through the bookshelves of libraries across the world.

Our praise and gratitude go to the many authors who donated their time and expertise to this book—and a very special thank you goes to our section editors, Merlin G. Butler, MD, PhD, Phillip D.K. Lee, MD, and Barbara Y. Whitman, PhD, and to our managing editor, Linda Keder. Hopefully, I will be around long enough to be able to say someday, “My goodness, that third edition was certainly dismal!” May each generation step on the shoulders of the last, to peer over the wall of reality of their day in order to view a brighter future for their chil- dren with PWS.

Janalee Heinemann, MSW

Executive Director, Prader-Willi Syndrome Association (USA)

x ^Preface

Acknowledgments

xi The editors wish to express their appreciation to the many colleagues

who contributed their time and expertise in authoring chapters for this edition of Management of Prader-Willi Syndrome. We have benefi ted from our interactions with each of the authors before and during the produc- tion of the book and look forward to continued collaborations. The editors also thank Dr. Barbara Lippe for her personal and professional efforts in improving the recognition and treatment of individuals with PWS and the leadership of both the Prader-Willi Syndrome Association (USA) and the International Prader-Willi Syndrome Organization (IPWSO) for their advocacy and their ongoing support of this project.

We wish to express our special thanks to all of the patients and their families with whom we have interacted over the years. These interac- tions have motivated us to strive harder in gaining a better understand- ing of the causes of Prader-Willi syndrome and in developing treatment plans to assist those affected. We are grateful to them for teaching us about the condition and how it impacts on their daily lives.

The editors would also like to thank the many individuals who have provided outstanding assistance and motivation in completing this book, including assistants and colleagues in our individual workplaces.

We are indebted to Linda Keder, managing editor, for her guidance and enormous hard work. Her untiring nature and meticulous skills for perfection have led us along the journey from the planning stage to revising and editing of this edition. Her skills as an established editor and her dedication and commitment to excellence are unsurpassed. We also would like to thank Janalee Heinemann, executive director of PWSA (USA), for her patience with us as editors and for her dedication to completing tasks in a timely fashion. We would be remiss if we did not acknowledge Paula Callaghan, senior editor of the clinical medi- cine section at Springer SBM publishers. Her experience and wealth of information about the publishing process have been very helpful.

Lastly, our deepest gratitude goes to our respective families for their

support and encouragement during the many hours spent in the pro-

duction of this book. Much of the time required for writing and editing

occurred at the end of the day when our other job responsibilities were

fi nished. In addition, we appreciate their patience, support, and under- standing during all the years of our professional lives and in allowing us to enjoy the fruits of our labor.

Merlin G. Butler, MD, PhD

Phillip D.K. Lee, MD

Barbara Y. Whitman, PhD

xii Acknowledgments

Contents

xiii

Foreword I by Pamela F. Eisen . . . v

Foreword II by Giorgio Fornasier. . . vii

Preface by Janalee Heinemann . . . ix

Acknowledgments . . . xi

Contributors . . . xvii

Introduction by Louise R. Greenswag and Randell C. Alexander . . xxi

Part I Diagnosis and Genetics Chapter 1 Clinical Findings and Natural History of Prader-Willi Syndrome. . . 3

Merlin G. Butler, Jeanne M. Hanchett, and Travis Thompson Chapter 2 Diagnostic Criteria for Prader-Willi Syndrome . . . 49

Shawn E. McCandless and Suzanne B. Cassidy Chapter 3 Molecular Genetic Findings in Prader-Willi Syndrome. . . 58

Karin Buiting and Bernhard Horsthemke Chapter 4 Laboratory Testing for Prader-Willi Syndrome . . . 74

Kristin G. Monaghan and Daniel L. Van Dyke Part II Medical Physiology and Treatment Chapter 5 Medical Considerations in Prader-Willi Syndrome. . . 97

Urs Eiholzer and Phillip D.K. Lee Chapter 6 Gastrointestinal System, Obesity, and Body Composition . . . 153 Ann O. Scheimann, Phillip D.K. Lee, and

Kenneth J. Ellis

Chapter 7 Growth Hormone and Prader-Willi Syndrome . . . 201 Aaron L. Carrel, Phillip D.K. Lee, and

Harriette R. Mogul

Part III Multidisciplinary Management

Chapter 8 Neurodevelopmental and Neuropsychological

Aspects of Prader-Willi Syndrome . . . 245 Barbara Y. Whitman and Travis Thompson

Chapter 9 Speech and Language Disorders Associated with

Prader-Willi Syndrome. . . 272 Barbara A. Lewis

Chapter 10 Motor and Developmental Interventions . . . 284 Toni Goelz

Chapter 11 Educational Considerations for Children with

Prader-Willi Syndrome. . . 302 Naomi Chedd, Karen Levine, and

Robert H. Wharton

Chapter 12 Tools for Psychological and

Behavioral Management . . . 317 Barbara Y. Whitman and Kevin Jackson

Chapter 13 Educational and Social Issues for Adolescents

with Prader-Willi Syndrome . . . 344 Barbara J. Goff

Chapter 14 Transition from Adolescence to Young Adulthood: The Special Case of

Prader-Willi Syndrome. . . 356 Ellie Kazemi and Robert M. Hodapp

Chapter 15 Vocational Training for People with

Prader-Willi Syndrome. . . 370 Steve Drago

Chapter 16 Residential Care for Adults with

Prader-Willi Syndrome. . . 381 Mary K. Ziccardi

Chapter 17 Inpatient Crisis Intervention for Persons with

Prader-Willi Syndrome. . . 395 Linda M. Gourash, James E. Hanchett, and

Janice L. Forster

Chapter 18 Social Work Interventions: Advocacy and

Support for Families . . . 426 Barbara Y. Whitman

xiv ^Contents

Chapter 19 A National Approach to Crisis Intervention

and Advocacy . . . 440 David A. Wyatt

Chapter 20 Advocacy Issues: School Discipline

and Expulsion . . . 448 Barbara J. Goff

Chapter 21 Advocacy Issues: Sexuality . . . 457 Janalee Heinemann, David A. Wyatt,

and Barbara J. Goff

Appendices

A First Published Report of Prader-Willi Syndrome . . . 467 B A Comprehensive Team Approach to the Management

of Prader-Willi Syndrome . . . 473 Urs Eiholzer, Editor

C Growth Charts of Individuals with

Prader-Willi Syndrome . . . 487 D Eligibility for U.S. Social Security and SSI Benefi ts for

Individuals with Prader-Willi Syndrome . . . 504 Barbara R. Silverstone

E The International Prader-Willi Syndrome Organization . . . . 514 F The Prader-Willi Syndrome Association (USA) . . . 529

Index . . . 535

xv

Contents ^xv

Contributors

xvii Randell C. Alexander, MD, PhD

Professor of Clinical Pediatrics, Morehouse School of Medicine, Department of Pediatrics, Atlanta, GA 30310, USA

Karin Buiting, PhD

Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany

Merlin G. Butler, MD, PhD

Chief, Section of Medical Genetics and Molecular Medicine, William R.

Brown/Missouri Chair of Medical Genetics and Molecular Medicine;

Professor of Pediatrics, University of Missouri-Kansas City School of Medicine, Children’s Mercy Hospitals and Clinics, Kansas City, MO 64108, USA

Aaron L. Carrel, MD

Associate Professor of Pediatrics, University of Wisconsin Medical School, Madison, WI 53792, USA

Suzanne B. Cassidy, MD

Clinical Professor of Pediatrics, University of California, Irvine, Orange, CA 92868, USA

Naomi Chedd, MS, LMHC

Education Consultant and Mental Health Counselor in private practice, Brookline, MA 02446, USA

Steve Drago, BS, CABA

Associate Director, ARC of Alachua County, Gainesville, FL 32606, USA

Urs Eiholzer, MD

Director, Institute Growth Puberty Adolescence, Zürich, Switzerland

Pamela F. Eisen

President, International Prader-Willi Syndrome Organization (IPWSO), Wormleysburg, PA 17043, USA

Kenneth J. Ellis, PhD

Professor of Pediatrics and Director, Body Composition Laboratory, Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA

Giorgio Fornasier

Director of Program Development, International Prader-Willi Syn- drome Organization (IPWSO), 32020 Limana, Italy

Janice L. Forster, MD

Former Consulting Psychiatrist, The Children’s Institute Prader-Willi Syndrome and Behavior Disorders Program; Physician in private practice, Pittsburgh, PA 15228, USA

Toni Goelz, BS

Staff Physical Therapist, Cardinal Glennon Children’s Hospital, St.

Louis, MO 63104, USA Barbara J. Goff, EdD

Consultant for Prader-Willi Syndrome; Assistant Professor of Educa- tion, Westfi eld State College, Westfi eld, MA 01086, USA

Linda M. Gourash, MD

Formerly Chief Attending Physician, The Children’s Institute Prader- Willi Syndrome and Behavior Disorders Program; Physician in private practice, Pittsburgh, PA 15228, USA

Louise R. Greenswag, RN, PhD

Consultant for Prader-Willi Syndrome, Division of Developmental and Behavioral Medicine, Center for Disabilities and Development, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA James E. Hanchett, MD

Formerly Consultant to The Children’s Institute Prader-Willi Syndrome and Behavior Disorders Program, Pittsburgh, PA 15217, USA

Jeanne M. Hanchett, MD

Assistant Professor, Department of Pediatrics, University of Pittsburgh School of Medicine; The Children’s Institute of Pittsburgh, Pittsburgh, PA 15217, USA

xviii Contributors

†

Deceased.

Janalee Heinemann, MSW

Executive Director, Prader-Willi Syndrome Association (USA), Sarasota, FL 34242, USA

Robert M. Hodapp, PhD

Co-Director, Family Research Program, Vanderbilt Kennedy Center;

Professor, Special Education, Peabody College, Nashville, TN 37203, USA

Bernhard Horsthemke, PhD

Professor of Human Genetics, Institut für Humangenetik, Universitäts- klinikum Essen, Essen, Germany

Kevin Jackson, PhD, BCBA

Senior Behavior Analyst, Agency for Persons with Disabilities, Gainesville, FL 32602, USA

Ellie Kazemi

Graduate Student, Psychological Studies in Education, University of California, Los Angeles, Graduate School of Education and Information Studies, Los Angeles, CA 90095, USA

Phillip D.K. Lee, MD

Formerly Professor of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; currently Chief Scientifi c Offi cer, Immunodiagnostic Systems Ltd., Boldon, Tyne and Wear, NE 35 9PD, UK

Karen Levine, PhD

Clinical Director, Autism Services, North Shore ARC, Danvers, MA 01923, USA

Barbara A. Lewis, PhD, CCC–SLP

Associate Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University, Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA

Shawn E. McCandless, MD

Assistant Professor, Genetics and Pediatrics, Center for Human Genetics, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA

Harriette R. Mogul, MD, MPH

Professor of Medicine, Chief, Section of Obesity and Osteoporosis, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA

Contributors ^xix

Kristin G. Monaghan, PhD

Director, DNA Diagnostic Laboratory, Department of Medical Genetics, Henry Ford Hospital and Medical Center, Detroit, MI 48202, USA Ann O. Scheimann, MD

Assistant Professor of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD 21287; Adjunct Assistant Professor of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA

Barbara R. Silverstone, JD

Staff Attorney, National Organization of Social Security Claimants’

Representatives, Englewood Cliffs, NJ 07632, USA Travis Thompson, PhD

Executive Program Director, Minnesota Autism Center, Minneapolis, MN 55413, USA

Daniel L. Van Dyke, PhD

Co-Director, Cytogenetics Laboratory, Mayo Clinic, Rochester, MN 55905, USA

Robert H. Wharton, MD

Spalding Rehabilitation Hospital, Boston, MA 02114, USA Barbara Y. Whitman, PhD

Professor of Pediatrics, Saint Louis University School of Medicine, Car- dinal Glennon Children’s Hospital, St. Louis, MO 63104, USA

David A. Wyatt

Crisis Intervention Counselor, Prader-Willi Syndrome Association (USA), Sarasota, FL 34242, USA

Mary K. Ziccardi, BS

Administrator, The MENTOR Network, REM Ohio, Inc., Cleveland, OH 44125, USA

xx Contributors

†

Deceased.

Introduction

Why a third edition of Management of Prader-Willi Syndrome? The purpose remains the same as that of previous editions, to reach profes- sionals, parents, and extended families—virtually anyone interested in learning about Prader-Willi syndrome (PWS). And, since the last edition was published, there have been major advances in clinical management and research into the complex issues associated with this syndrome.

Genetic tests ensure identifi cation with 99% accuracy, endocrine studies have shown the benefi ts of growth hormone therapy, and innovative strategies are being designed to enhance psychosocial adaptation. Pro- fessionals and parents of affected children now have more in-depth knowledge, recognize the long-term consequences of this condition, and share common goals.

A historical backdrop provides a perspective on what has transpired since PWS was fi rst described in 1956 and how far knowledge has progressed. For more than 30 years after being identifi ed, only the major features were recognized. No cause was known. Few physicians had heard of it. The obesity was considered uncontrollable and life expectancy short. Children presented then—as now—as limp, sleepy, non-responsive babies, who are poor eaters and slow to achieve devel- opmental milestones. Typically, doctors might have found a paragraph or two about PWS in a few medical references but little about manage- ment. Diagnosis was made by clinical evaluation. Most individuals were identifi ed late in childhood if at all. Management was often mediocre.

During the 1980s several important events occurred. Holm, Sulzbacher, and Pipes published the book Prader-Willi Syndrome, a compendium of comprehensive fi ndings from a conference on the syndrome in 1981. That same year, Dr. David Ledbetter discovered the deletion of information on the 15th chromosome in some affected individuals. In 1983, Dr. Merlin Butler recognized that the deletion causing PWS occurred in the chromosome 15 inherited from the father.

Six years later, Dr. Robert Nicholls identifi ed uniparental disomy 15 (both 15s from the mother) as the genetic explanation for most of

xxi

the phenotypically similar subjects without the chromosome 15 deletion and proposed the role of genomic imprinting.

Even though scientifi c research advanced and descriptive articles about PWS appeared in the literature, bewildered parents continued to struggle to fi nd help. In 1987, when we established a PWS clinic at the University of Iowa to serve families, it became clear that case manage- ment was limited and fragmented in scope. Professionals as well as families needed an additional resource. The challenge was to determine what information would be most valuable. What we originally con- ceived as a small booklet of facts to explain PWS to the parents attend- ing the clinic evolved into the fi rst edition of Management of Prader-Willi Syndrome. Welcomed and fully supported by the Prader-Willi Syn- drome Association (USA), the success of this fi rst volume received worldwide distribution due, in large part, to the leading authorities that contributed chapters. Seven years later, burgeoning research in genetics, endocrinology, the use of psychotropic medications, and inno- vative approaches to management led to the publication of the second volume. This third edition is an indication that the boundaries of what is known about PWS have expanded even further.

The multifaceted characteristics of PWS remain the same. The syn- drome is an eating rather than a weight disorder; the overpowering hunger is a physiological fact of life. And, unlike those with exogenous obesity, most persons with PWS never feel full. Diffi culties arise when this lack of satiety is compounded by the fact that most affected indi- viduals do not have the cognitive capacity to comply with unsuper- vised food intake regimens. Furthermore, while food issues are a critical component of management, equally important are the emotional and cognitive features that affect how individuals think, feel, and react.

Children, usually affable and compliant until late toddlerhood, tend to become emotionally labile as they grow older, demonstrating aberrant behaviors, regardless of the presence or absence of obesity. With appro- priate nutritional management, those who previously would have died young due to obesity now live well into adulthood and, with their families, confront issues as developmentally disabled adults that require comprehensive, sensitive management.

As with any condition, diagnosis is merely the beginning. Ongoing case management tailored to the needs of children with PWS and their families is essential. For example, recognition early in life can lead to specifi c strategies to augment developmental milestones. Recognizing this struggle, the U.S. national parent organization, the Prader-Willi Syndrome Association (USA) is helping bridge the gap between parents and professionals by initiating the learning process. With knowledge of what typically happens and possible variations on this theme, fre- quently noted concerns may be anticipated and ameliorated.

The text of this new edition has been divided into three sections:

Part I: Diagnosis and Genetics, edited by Merlin G. Butler, MD, PhD, explains and discusses the complex genetics of PWS and procedures for clinical and genetic diagnostic evaluations, as well as providing an overview of the clinical fi ndings and natural history of PWS.

xxii Introduction

Part II: Medical Physiology and Treatment, edited by Phillip D.K. Lee, MD, provides an overview of medical issues and management across the life span, with separate chapters devoted to growth hormone issues and treatment and to gastrointestinal issues, obesity, and body composition.

Part III: Multidisciplinary Management, edited by Barbara Y. Whitman, PhD, focuses on the neurodevelopmental, neurocognitive, and devel- opmental aspects of PWS and the accompanying life span management issues, including behavior and crisis management, educational con- cerns, and vocational and residential options.

We believe that this book, edited and written by the very best in the fi eld and updated with the latest research, is likely to be the single best resource of information and support for the next several years. There is no yardstick to measure the challenges that these children and their families face, but professionals and parents alike will be able to achieve a depth of understanding and grasp of details about PWS that were an unachievable dream only two decades ago. Although we have come far, there is still no magic cure. We are hopeful that a genetic interven- tion will eventually be found.

Louise R. Greenswag, RN, PhD Randell C. Alexander, MD, PhD Editors, Management of Prader-Willi Syndrome, First and Second

Editions

Introduction ^xxiii