Juvenile Huntington's disease : (and other trinucleotide repeat disorders) PDF
Preview Juvenile Huntington's disease : (and other trinucleotide repeat disorders)
J uvenile Huntington’s disease This page intentionally left blank J uvenile Huntington’s disease (and other trinucleotide repeat disorders) E dited by O liver W. J. Quarrell H elen M. Brewer F erdinando Squitieri R oger A. Barker M artha A. Nance G . Bernhard Landwehrmeyer 1 1 Great Clarendon Street, Oxford ox2 6dp Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide in Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries Published in the United States by Oxford University Press Inc., New York © Oxford University Press 2009 The moral rights of the author have been asserted Database right Oxford University Press (maker) First published 2009 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, or under terms agreed with the appropriate reprographics rights organization. Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above You must not circulate this book in any other binding or cover and you must impose this same condition on any acquirer A catalogue record for this title is available from the British Library Data available Library of Congress Cataloguing in Publication Data Data available Typeset in Minion by Cepha Imaging Private Ltd., Bangalore, India Printed in Great Britain on acid-free paper by Biddles Ltd., King’s Lynn, UK ISBN 978–0–19–923612–1 10 9 8 7 6 5 4 3 2 1 D edication This book is dedicated to all young people with juvenile Huntington’s disease (JHD) and their families, especially those who have contributed to this book or who were in the minds of the authors who contributed. This page intentionally left blank P reface W hy study juvenile Huntington’s disease? J uvenile Huntington’s disease (JHD) is not a separate entity and, as will be clear in this book, the definition of onset before the age of 20 years is a convenience rather than a representation of a biological phenome- non. JHD is a way of describing one end of the phenotypic spectrum of HD. There have been studies, although few in number, focusing on JHD; in addition, JHD is mentioned in books, book chapters, and other, more general, studies of HD. Given this, why a book devoted to JHD? T his project started following the formation of the European Huntington’s Disease Network (EHDN). A number of working groups were formed within the EHDN, one of which was on JHD. The working group identified the need to gather information on this aspect of HD in one place. To that end, an international meeting was convened in London in November 2006; this formed the basis for the book. It does mean that we have a starting point for clinicians who care for families with the juvenile form of HD; in addition it should be a starting point for researchers in identifying what is already known; more importantly, this project has identified gaps in our knowledge. C linicians interested in HD, laboratory based and social scientists, together with members of the patients’ organizations form a commu- nity. There has always been a close relationship between clinicians, sci- entists and patients’ organizations, with meetings frequently involving all of the above groups. This valuable working relationship is reflected in this book, with the first two chapters being contributions from one person with JHD and a number of parents/carers describing their per- spective of the condition. Personal accounts of HD exist, but it is par- ticularly useful to gather in one place accounts specifically about JHD. Listening to, or reading, the experiences of patients and families is a valuable method of extending knowledge and learning. viii PREFACE T he first few chapters focus on historical, clinical, and pathological features of JHD. The next chapters have a more basic scientific nature. It is important to realize that HD is part of a family of related disorders characterized by an expansion of a CAG repeat sequence in the coding part of the gene, so it is relevant to consider juvenile onset in these con- ditions. The later chapters return to more clinical matters and areas for future development, such as delays in reaching a diagnosis, psychoso- cial issues, and problems with clinical rating scales. I n recent years, much has been learnt from animal models of HD; the overwhelming majority have very large expansions of the trinucleotide CAG repeat mutation and can be said to be modelling the juvenile form of the condition. We can anticipate future therapeutic interventions being evaluated in these animal models. It is timely to draw together information on those with young onset HD, many of whom also have large trinucleotide repeat expansions. Currently, there are no evi- denced-based guidelines for the management of JHD. JHD is relatively rare, but with the use of web-based technology and international research networks in Europe, North America, and elsewhere we can start to address some of the gaps in our knowledge. The development of reliable relevant rating scales is essential for including patients at the young onset end of the phenotypic spectrum in intervention studies. This is going to be crucial as and when we have treatments which poten- tially alter the natural history of the condition. We need to be in a posi- tion both to develop evidenced-based guidelines and to evaluate future interventions for younger affected patients. Summarizing our current knowledge of JHD in this book is one part of realizing that goal. O liver W. J. Quarrell Foreword: Juvenile Huntington’s Disease By Nancy S. Wexler, Ph.D. Huntington’s disease is one of the most common Mendelian genetic diseases in the world. Its prevalence includes those who are currently symptomatic as well as those destined to develop symptoms in the future. In Europe, Australia, New Zealand and the Americas, its preva- lence is about 1 in 10,000 individuals who demonstrate symptoms at any one time. But twice that number will become symptomatic in the future. In the European Union, Huntington’s disease affects approximately 150,000 to 200,000 individuals and in the U.S. about 100,000 people. One-third of these people are individuals who currently have symp- toms. The other two-thirds are carrying a copy of the expanded, abnor- mal HD gene and will eventually, and inevitably, develop symptoms in the future. Of all Huntington’s disease gene-carriers, about 10% will develop symptoms after age 60 years old and about 10% will follow the wrenching path of juvenile onset. Everything aches in us when we see a child who is sick. Children who suffer from juvenile Huntington’s disease are often the exact opposite of their adult counterparts – even their parents. Instead of the wild, flailing movements of all parts of the body, known as chorea, children with juvenile Huntington’s disease are like tiny automatons, rigid in all parts of their bodies. Their movements are stiff and slow – like wooden puppets. Their eyes are dipped in glue. They can barely move their pupils from side to side. And their facial expressions are frozen in wax. Once they start to smile, it takes forever to fully bloom and cover their faces. And then it slowly fades, like the Cheshire cat. Even though some adults with Huntington’s disease develop symptoms of rigidity and slowness, occasionally toward the end of their illness,
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