GARDNER AND SUTHERLAND’S CHROMOSOME ABNORMALITIES AND GENETIC COUNSELING 2 OXFORD MONOGRAPHS ON MEDICAL GENETICS General Editors: JUDITH G. HALL PETER S. HARPER LOUANNE HUDGKINS EVAN EICHLER CHARLES J. EPSTEIN (DECEASED 2011) ARNO G. MOTULSKY (RESIGNED 2011) 1. R. B. McConnell: The genetics of gastrointestinal disorders 2. A. C. Kopéc: The distribution of the blood groups in the United Kingdom 3. E. Slater and V. A. Cowie: The genetics of mental disorders 4. C. O. Carter and T. J. Fairbank: The genetics of locomotor disorders 5. A. E. Mourant, A. C. Kopéc, and K. Domaniewska-Sobezak: The distribution of the human blood groups and other polymorphisms 6. A. E. Mourant, A. C. Kopéc, and K. Domaniewska-Sobezak: Blood groups and diseases 7. A. G. Steinbert and C. E. Cook: The distribution of the human immunoglobulin allotypes 8. D. Tills, A. C. Kopéc, and R. E. Tills: The distribution of the human blood groups and other polymorphisms: Supplement I 10. D. Z. Loesch: Quantitative dermatoglyphics: Classification, genetics, and pathology 11. D. J. Bond and A. C. Chandley: Aneuploidy 12. P. F. Benson and A. H. Fensom: Genetic biochemical disorders 13. G. R. Sutherland and F. Hecht: Fragile sites on human chromosomes 14. M. d’A Crawfurd: The genetics of renal tract disorders 16. C. R. Scriver and B. Child: Garrod’s inborn factors in disease 18. M. Baraitser: The genetics of neurological disorders 19. R. J. Gorlin, M. M. Cohen, Jr., and L. S. Levin: Syndromes of the head and neck, third edition 21. D. Warburton, J. Byrne, and N. Canki: Chromosome anomalies and prenatal development: An atlas 22. J. J. Nora, K. Berg, and A. H. Nora: Cardiovascular disease: Genetics, epidemiology, and prevention 24. A. E. H. Emery: Duchenne muscular dystrophy, second edition 25. E. G. D. Tuddenham and D. N. Cooper: The molecular genetics of haemostasis and its inherited disorders 26. A. Boué: Foetal medicine 27. R. E. Stevenson, J. G. Hall, and R. M. Goodman: Human malformations 28. R. J. Gorlin, H. V. Toriello, and M. M. Cohen, Jr.: Hereditary hearing loss and its syndromes 29. R. J. M. Gardner and G. R. Sutherland: Chromosomes abnormalities and genetic counseling, second edition 30. A. S. Teebi and T. I. Farag: Genetic disorders among Arab populations 31. M. M. Cohen, Jr.: The child with multiple birth defects 32. W. W. Weber: Pharmacogenetics 3 33. V. P. Sybert: Genetic skin disorders 34. M. Baraitser: Genetics of neurological disorders, third edition 35. H. Ostrer: Non- Mendelian genetics in humans 36. E. Traboulsi: Genetic factors in human disease 37. G. L. Semenza: Transcription factors and human disease 38. L. Pinsky, R. P. Erickson, and R. N. Schimke: Genetic disorders of human sexual development 39. R. E. Stevenson, C. E. Schwartz, and R. J. Schroer: X- linked mental retardation 40. M. J. Khoury, W. Burke, and E. Thomson: Genetics and public health in the 21st century 41. J. Weil: Psychosocial genetic counseling 42. R. J. Gorlin, M. M. Cohen, Jr., and R. C. M. Hennekam: Syndromes of the head and neck, fourth edition 43. M. M. Cohen, Jr., G. Neri, and R. Weksberg: Overgrowth syndromes 44. R. A. King, J. I. Rotter, and A. G. Motulsky: Genetic basis of common diseases, second edition 45. G. P. Bates, P. S. Harper, and L. Jones: Huntington’s disease, third edition 46. R. J. M. Gardner and G. R. Sutherland: Chromosome abnormalities and genetic counseling, third edition 47. I. J. Holt: Genetics of mitochondrial disease 48. F. Flinter, E. Maher, and A. Saggar- Malik: Genetics of renal disease 49. C. J. Epstein, R. P. Erickson, and A. Wynshaw-Boris: Inborn errors of development: The molecular basis of clinical disorders of morphogenesis 50. H. V. Toriello, W. Reardon, and R. J. Gorlin: Hereditary hearing loss and its syndromes, second edition 51. P. S. Harper: Landmarks in medical genetics 52. R. E. Stevenson and J. G. Hall: Human malformations and related anomalies, second edition 53. D. Kumar and S. D. Weatherall: Genomics and clinical medicine 54. C. J. Epstein, R. P. Erickson, and A. Wynshaw-Boris: Inborn errors of development: The molecular basis of clinical disorders of morphogenesis, second edition 55. W. Weber: Pharmacogenetics, second edition 56. P. L. Beales, I. S. Farooqi, and S. O’Rahilly: The genetics of obesity syndromes 57. P. S. Harper: A short history of medical genetics 58. R. C. M. Hennekam, I. D. Krantz, and J. E. Allanson: Gorlin’s syndromes of the head and neck, fifth edition 59. D. Kumar and P. Elliot: Principles and practices of cardiovascular genetics 60. V. P. Sybert: Genetic skin disorders, second edition 61. R. J. M. Gardner, G. R. Sutherland, and L. C. Shaffer: Chromosome abnormalities and genetic counseling, fourth edition 62. D. Kumar: Genomics and health in the developing world 63. G. Bates, S. Tabrizi, and L. Jones: Huntington’s disease, fourth edition 4 64. B. Lee and F. Scaglia: Inborn errors of metabolism: From neonatal screening to metabolic pathways 65. D. Kumar and C. Eng: Genomic medicine, second edition 66. R. Stevenson, J. Hall, D. Everman, and B. Solomon: Human malformations and related anomalies, third edition 67. R. Erickson and A. Wynshaw-Boris: Epstein’s inborn errors of development: The molecular basis of clinical disorders of morphogenesis, third edition 68. C. Hollak and R. Lachmann: Inherited metabolic disease in adults: A clinical guide 69. V. P. Sybert: Genetic skin disorders, third edition 70. R. J. M. Gardner and D. J. Amor: Gardner and Sutherland’s chromosome abnormalities and genetic counseling, fifth edition 5 GARDNER AND SUTHERLAND’S Chromosome Abnormalities and Genetic Counseling FIFTH EDITION R. J. McKinlay GARDNER ADJUNCT PROFESSOR CLINICAL GENETICS GROUP UNIVERSITY OF OTAGO, DUNEDIN, NEW ZEALAND David J. AMOR LORENZO AND PAMELA GALLI CHAIR UNIVERSITY OF MELBOURNE VICTORIAN CLINICAL GENETICS SERVICES MURDOCH CHILDREN’S RESEARCH INSTITUTE ROYAL CHILDREN’S HOSPITAL, MELBOURNE, AUSTRALIA 6 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 certain other countries. Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America. © Oxford University Press 2018 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 license, or under terms agreed with the appropriate reproduction rights organization. Inquiries 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. Library of Congress Cataloging-in-Publication Data Names: Gardner, R. J. M., author. | Amor, David J., author. Title: Gardner and Sutherland’s chromosome abnormalities and genetic counseling / R. J. McKinlay Gardner, David J. Amor. Other titles: Chromosome abnormalities and genetic counseling | Oxford monographs on medical genetics ; no. 70. Description: Fifth edition. | Oxford ; New York : Oxford University Press, [2018] | Series: Oxford monographs on medical genetics ; no. 70 | Preceded by Chromosome abnormalities and genetic counseling / R.J. McKinlay Gardner, Grant R. Sutherland, Lisa G. Shaffer. c2012. | Includes bibliographical references and index. Identifiers: LCCN 2017034126 | ISBN 9780199329007 (hardcover : alk. paper) | ISBN 9780199329021 (epub) Subjects: | MESH: Chromosome Aberrations | Genetic Counseling Classification: LCC RB155.7 | NLM QS 677 | DDC 616/.042—dc23 LC record available at https://lccn.loc.gov/2017034126 This material is not intended to be, and should not be considered, a substitute for medical or other professional advice. Treatment for the conditions described in this material is highly dependent on the individual circumstances. And, while this material is designed to offer accurate information with respect to the subject matter covered and to be current as of the time it was written, research and knowledge about medical and health issues is constantly evolving and dose schedules for medications are being revised continually, with new side effects recognized and accounted for regularly. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulation. The publisher and the authors make no representations or warranties to readers, express or implied, as to the accuracy or completeness of this material. Without limiting the foregoing, the publisher and the authors make no representations or warranties as to the accuracy or efficacy of the drug dosages mentioned in the material. The authors and the publisher do not accept, and expressly disclaim, any responsibility for any liability, loss or risk that may be claimed or incurred as a consequence of the use and/or application of any of the contents of this material. 7 This book is dedicated to Jocelyn, Geoffrey, and Craig, their parents, and all other families who seek our “chromosomal advice.” Jocelyn and Geoffrey (with lamb) have a partial trisomy for chromosome 4 long arm, and Craig, the youngest, had a 46,XY result on amniocentesis. Their father is a translocation carrier (see Fig. 5–1, lower). Craig, since married, came to the genetic clinic 8 for confirmatory advice about his low genetic risk. 9 Heredity Inescapably, this is me—the diagnosis is cause for anger at those who brightly say we choose our destinies. There is no store of courage, wit or will can save me from myself and I must face my children, feeling like that wicked fairy, uninvited at the christening, bestowing on my own, amidst murmurs of apprehension, a most unwanted gift—that of a blighted mind. No one could tell me of this curse when I was young and dreamt of children and the graces they would bear. Later, it seemed that a chill morning revealed deeper layers of truth. For my romancing there is a price to pay— perhaps my children’s children will pass this tollgate after me. My grandmothers gaze down from their frames on my wall, sadly wondering. —Meg Campbell Dear DNA In real life you’re just a tangle of white filaments captured in a test-tube, and your first photo is not flattering: grey smudges like tractor tracks, or a rusty screw. Yet many say you are beautiful. Online for a night with a hundred fantastic portraits 10