Table Of Contenti
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
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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
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1
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First Edition published in 2005
Second Edition published in 2017
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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 chal-
lenge 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
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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
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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.
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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 tremen-
dous 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.
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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
