Table Of Content

i OXFORD MEDICAL PUBLICATIONS Oxford Desk Reference Clinical genetics and genomics ii Oxford Desk Reference: Acute Medicine Oxford Desk Reference: Obstetrics and Edited by Richard Leach, Derek Bell, and Kevin Moore Gynaecology Edited by Sabaratnam Arulkumaran, Lesley Regan, Oxford Desk Reference: Cardiology Aris Papageorghiou, Ash Monga, and David Farquharson Edited by Hung-Fat Tse, Gregory Y. Lip, and Andrew J. Stewart Coats Oxford Desk Reference: Oncology Edited by Thankamma V. Ajithkumar, Ann Barrett, Oxford Desk Reference: Clinical Genetics 2e Helen Hatcher, and Natalie Cook Helen V. Firth and Jane A. Hurst Oxford Desk Reference: Respiratory Medicine Oxford Desk Reference: Critical Care Edited by Nick Maskell and Ann Millar Carl Waldmann, Neil Soni, and Andrew Rhodes Oxford Desk Reference: Rheumatology Oxford Desk Reference: Geriatric Medicine Edited by Richard Watts, Gavin Clunie, Frances Hall, and Edited by Margot Gosney, Adam Harper, and Tarnya Marshall Simon Conroy Oxford Desk Reference: Toxicology Oxford Desk Reference: Major Trauma Edited by D. Nicholas Bateman, Robert D. Jefferson, Edited by Jason Smith, Ian Greaves, and Keith Porter Simon H. L. Thomas, John P. Thompson, and J. Allister Vale Oxford Desk Reference: Nephrology Jonathan Barratt, Kevin Harris, and Peter Topham iii Oxford Desk Reference Clinical genetics and genomics Second Edition Helen V. Firth Consultant in Clinical Genetics, Cambridge University Hospitals, Cambridge, UK and Hon Faculty Member, Wellcome Trust Sanger Institute, Hinxton, UK Jane A. Hurst Consultant in Clinical Genetics, Great Ormond Street Hospital, London, UK 1 iv 1 Great Clarendon Street, Oxford, OX2 6DP, United Kingdom 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. Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries © Oxford University Press 2017 The moral rights of the authors have been asserted First Edition published in 2005 Second Edition published in 2017 Impression: 1 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, by licence 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 work in any other form and you must impose this same condition on any acquirer Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America British Library Cataloguing in Publication Data Data available Library of Congress Control Number: 2016958194 ISBN 978– 0– 19– 955750– 9 Printed and bound by CPI Group (UK) Ltd, Croydon, CR0 4YY Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-t o- date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work. Except where otherwise stated, drug dosages and recommendations are for the non-p regnant adult who is not breast- feeding Links to third party websites are provided by Oxford in good faith and for information only. Oxford disclaims any responsibility for the materials contained in any third party website referenced in this work. v v Preface to the second edition Welcome to the second edition of Oxford Desk Reference: Clinical Genetics and Genomics. We were surprised and delighted by the amazingly positive response to the first edition and apologize to readers who have been eagerly awaiting the second edition that it has taken so long to reach publication. Since sending the first edition to press, Helen has become Clinical Lead for DECIPHER (http:// decipher.sanger.ac.uk) and the Deciphering Developmental Disorders (DDD) study (http:// www.ddduk.org), and Jane became Clinical Lead for Genetics at Great Ormond Street Hospital, London. While these roles have kept us both very busy, they have expanded our network of Expert Advisers and clinical practice and we hope you will see the benefits of that in this new edition. Like many of our readers, we are learning how to navigate the opportunities and chal- lenges of the new sequencing technologies that have led to an explosion in knowledge and potential for diagnosis. Establishing safe models of practice that reap the diagnostic benefits, while minimizing the potential harms of misdiagnosis and overdiagnosis, is a challenge for all working in clinical genetics. Addressing that challenge is essential if we are to offer up-t o-d ate and accurate advice to patients and their families. We hope that this new edition, revised throughout from a genomic perspective, will help in that endeavour. Helen Firth and Jane Hurst vi vi Preface to the first edition When Helen and Jane asked me whether a desk reference in clinical genetics would be useful, I enthusiastically replied ‘yes’. Who has not been asked to see a child on the ward and not been able to remember the approach to a relatively common, but recently forgotten, disorder? During an outreach clinic, you are scheduled to see a family with a common disorder and they turn out to have two or three rare complications, and you do not have access to ‘real’ textbooks. You get a call from a good colleague who asks you ‘simple’ questions about the workings of a well-k nown syndrome and you do not want to appear stupid to your friend. This book can be your ‘lifesaver’ in many situations. The book includes many common- sense approaches, useful standards and definitions, suggestions for appropriate testing, and excellent references. It is meant to be ‘first line’ and a way to jog your memory. Certainly, you will need to consult other texts and data sources. However, this book can be carried around in your briefcase or handbag— so to speak a peripheral brain. Blank pages are distributed throughout the book to enable you to update and personalize your copy with notes from current journals, guidelines, seminars, and lectures. If it turns out to be useful, and I certainly expect that it will, there will surely be add- itional editions. The authors would therefore like feedback and suggestions. Genetic information is changing so quickly that a 2- year half- life can be expected. Medical genetics registrars, residents, and fellows should particularly find this book useful, but I would anticipate that the mature and experienced clinical geneticist would also find it useful and thoughtfully constructed. If you are the lucky new purchaser of Oxford Desk Reference: Clinical Genetics— ‘congratulations’. If you are considering buying it—‘ do it’. If you need an easy-t o- use, handy reference that can be carried around so you appear more competent and well informed— ‘don’t hesitate’. Enjoy this new approach. Judith G. Hall, OC, MD, FRCP(C), FAAP, FCCMG, FABMG Emeritus Professor of Pediatrics and Medical Genetics, University of British Columbia, Vancouver, Canada vii vii Acknowledgements In writing this book, we are indebted to the many colleagues and friends who have kindly given of their time and expertise to review each section of the book. Their wide experi- ence of particular clinical areas has enhanced the book in many ways, improving accuracy and clarity and ensuring that the entries are as up-t o- date as we can make them. We owe special thanks to our Cancer chapter expert advisers Marc Tischkowitz and Ian Frayling. We would also like to thank Rebecca Firth and Hannah Firth for their work as editorial assistants. Thanks also to Fiona Richardson at Oxford University Press for her commitment to this project over several years and special thanks to Fiona Chippendale for overseeing the production of the book. We also owe a debt of gratitude to Judy Hall for her sustained encouragement and enthusiasm and enormous thanks to our husbands and children for their love and forbearance. viii viii Reviews Published reviews of the first edition ‘… a comprehensive and highly focussed guide to clinical genetics that should certainly rank as an indispensable handbook for consultants in clinical genetics, genetic counsel- lors and paediatricians. However, it should also be extremely useful for PhD students in nearly all disciplines within medical and/ or human genetics. Its major strength is the well- conceived and clearly laid out format which enables the reader to obtain a rapid yet quite substantial overview of a plethora of difficult topics …’ Human Genetics ‘The authors of [this book] deserve to be congratulated for achieving the impossible… Overall this book is a winner and is a must for every clinical genetics department. This is arguably the most important book ever published for trainees in genetics…[but] can be considered as an extremely useful reference source to any genetics physician…this book is a 'peripheral brain' and 'lifesaver' for geneticists in many situations!’ Ulster Medical Journal Vol 75, no 3 ‘If there was a Booker Prize for new texts on clinical genetics, then the winner this year would be a foregone conclusion. No one else could possibly come up with an entry as good as this.… the definitive hands- on guide to clinical genetics .… The breadth and depth of information provided is remarkable. … As a practical guide to the specialty of clinical genetics this book has no match, and overall it represents an awesome achieve- ment. How did the authors manage to acquire and collate all this knowledge? Where did they find all this information? … If your department can only afford one book this year, make it this one. Better still, buy your own copy and keep it hidden because it is going to be much in demand.’ BMJ ‘This is an amazing compilation of genetic knowledge. It provides a fantastic tool for clinical geneticists who require a fast review of specific genetic subjects while performing clinical consultations.… Condensation of the amount of information included in this wonderful book could not be done any better.… This is a most- have tool for all clinical geneticists who require quick and specific reviews in clinical practice .… Dr Firth and Hurst have achieved a tremendous goal. They have been able to summarize a tremendous amount of information in clinical genetics and convert it to an excellent tool for the practice of the specialty. It could not be done any better. The magnificent work done suggests that as the field of clinical genetics expands, further editions will be needed. This is a must have book, and a second edition would be expected.’ Doody's Journal Pre- publication reviews of the first edition ‘It is very refreshing to review a book written for clinicians by clinicians, which is in a format that reflects situations actually encountered in practice. Information provided by the referring doctor to a clinical geneticist or other specialist before a clinic or ward consultation is usually limited. This new text takes common referral indications and, in a standardized format that manages to be brief and clear without skimping on detail, reminds the clinician of diagnostic possibilities and strategies for investigation and man- agement. This will allow the best possible use to be made of an individual consultation by both the patient and the doctor.’ Dian Donnai, Professor of Medical Genetics, University of Manchester, Consultant Clinical Geneticist, Regional Genetics Service, St Mary’s Hospital, Manchester, UK. ‘I have been impressed with the thoughtfulness of the topics. This should be a great help to many people who are part of the clinical genetics team…. There are up- to- date summaries for the staff member who needs a refresher, as well as the glossary and the headings on fundamental topics, like AD inheritance, for those just starting out.’ Lewis B. Holmes, Professor of Pediatrics, Harvard Medical School and Chief, Genetics and Teratology Unit, Massachusetts General Hospital for Children, Boston, Massachusetts, USA. ix ix Brief contents Detailed contents xi System- based contents xv Glossary of terms used in dysmorphology xix Glossary of genetic and genomic terms xxiv Abbreviations xxxv Chapter advisers xlviii Expert advisers xlix Expert advisers to the first edition liii 1 Introduction 1 2 Clinical approach 53 3 Common consultations 333 4 Cancer 541 5 Chromosomes 623 6 Pregnancy and fertility 703 Appendix 805 Index 863