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PDF eBook Study Guide Ebook
 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
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 twenty-first 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: The 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: The 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. H. V. Toriello and S. Smith: Hereditary hearing loss and its syndromes, third edition
Editors of Previous Editions of Hereditary Hearing Loss and Its Syndromes
First edition:
Robert J. Gorlin, Helga V. Toriello, and M. Michael Cohen, Jr.

Second edition:
Helga V. Toriello, William Reardon, and Robert J. Gorlin
HEREDITARY HEARING LOSS
AND ITS SYNDROMES
THIRD EDITION

EDITED BY

Helga V. Toriello
Shelley D. Smith

3
3
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Library of Congress Cataloging-in-Publication Data

Hereditary hearing loss and its syndromes / edited by Helga V. Toriello, Shelley D. Smith. — 3rd ed.
p. ; cm. — (Oxford monographs on medical genetics ; 63)
Includes bibliographical references and index.
ISBN 978–0–19–973196–1 (hardback : alk. paper) — ISBN 978–0–19–931388–4 (ebook)
I. Toriello, Helga V. II. Smith, Shelley D., 1949– III. Series: Oxford monographs on medical genetics ; no. 63.
[DNLM: 1. Hearing Disorders—genetics. 2. Abnormalities, Multiple—genetics. WV 270]
LC Classification not assigned
617.8′0642—dc23
2012049476

9 8 7 6 5 4 3 2 1
Printed in the United States of America
on acid-free paper
This book is dedicated to Drs. Robert Gorlin and
M. Michael Cohen, Jr., outstanding teachers, mentors,
and friends.
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 PREFACE

T
he previous edition of the book was published eight chapter; William Reardon for the endocrinology chapter
years ago; since then there has been an explosion in (as well as the chapters on syndrome diagnosis and genetic
the number of conditions for which the molecular counseling); Catherine Downs for the genetic counseling
basis has been found. To reflect that, we have included a chapter; and Michael Cohen Jr. for the chapters on syn-
subsection on molecular studies in each entry. We have drome delineation, genetic counseling, and musculoskel-
also eliminated descriptions of single case reports, espe- etal disorders. Of course, it goes without saying that Dr.
cially if they had been published more than two to three Robert Gorlin did the lion’s share of work on previous edi-
decades ago. There is an expanded chapter on embryology tions, as well as being the driving force behind this book.
of the ear and hearing apparatus, as well as new chapters Bob, I cannot thank you enough for trusting me to con-
on molecular diagnostic strategies for nonsyndromic hear- tinue the work you had started.
ing loss and on the genetic influences on non-Mendelian Finally, we would like to acknowledge the individuals
conditions such as adult-onset and noise-induced hearing who operated behind the scenes. We wish to thank most
loss. We hope the readers of this edition find this informa- of all Mary Fuller, our hospital librarian, whose jaw must
tion a useful addition. have dropped when she received my first batch of article
Throughout the book we tried to sort entities on a clin- requests, numbering over 150. My genetic counselors also
ical rather than molecular basis. That is why, for example, had to put up with my relative inaccessibility and occa-
Waardenburg syndrome type 1 and the syndrome of nasal sional crabbiness, and I thank them for their patience. Of
bone hypoplasia, hand contractures, and sensorineural course, my family merits some thanks, although admit-
hearing loss still have separate entries, even though both tedly my daughters were clueless when I worked on the
are caused by PAX3 mutations. Similarly, we did not lump second edition of this book. However, I am pleased that
into one entry all of the conditions caused by dominant they were dimly aware that I was working on this third edi-
or recessive mutations in GJB2, but rather kept them as tion, even though they are both long out of the home (and
separate entries. hopefully will remain that way).
Many colleagues contributed to this volume and Shelley Smith would like to thank her colleagues,
worked hard on their chapters. We are grateful to all of friends, and family who graciously put up with postpone-
them. We would also like to acknowledge the contribu- ment of everything else while she was immersed in writ-
tors to the previous editions who laid the groundwork for ing, and also thanks the UNMC McGoogan library for
several chapters: Kathleen Sulik and Douglas Cotanche digging up some obscure but important references. Most
for the embryology chapter; Judith Allanson for the exter- of all, we would like to thank the authors who created or
nal ear chapter; John Carey, Derin Westin, Maria Bitner- revised chapters to fit the new vision of this edition.
Glindzicz, Karen Heath, and Angel Campos-Barros for
the renal chapter; William Dobyns for the chapter on H. V. Toriello
nervous system disorders; Albert Schinzel for the chromo- Grand Rapids, Michigan
some chapter; Angela Lin for the cardiac chapter; Michael S. D. Smith
Netzloff and Rachel Fisher for the metabolic disorders Omaha, Nebraska

ix
This page intentionally left blank
 CONTENTS

Contributors xiii 10. GENETIC HEARING LOSS ASSOCIATED

WITH MUSCULOSKELETAL DISORDERS 322
1. GENETIC HEARING LOSS—A BRIEF HISTORY 1 Helga V. Toriello
†
Robert J. Gorlin and Helga V. Toriello
11. GENETIC HEARING LOSS ASSOCIATED
WITH RENAL DISORDERS 443
2. EPIDEMIOLOGY, ETIOLOGY, GENETIC MECHANISMS,
AND GENETIC COUNSELING 4 Judy Savige
Kathleen S. Arnos, Katherine O. Welch,
12. GENETIC HEARING LOSS ASSOCIATED WITH
and Arti Pandya
NEUROLOGICAL AND NEUROMUSCULAR DISORDERS 469
3. EMBRYOLOGY OF THE MAMMALIAN EAR 13 Martha A. Nance and Helga V. Toriello
Benjamin Kopecky and Bernd Fritzsch
13. GENETIC HEARING LOSS ASSOCIATED
WITH CARDIAC ABNORMALITIES 562
4. GENE/ENVIRONMENT INTERACTIONS IN
ACQUIRED HEARING LOSS 58 Holly H. Ardinger and Robert H. Ardinger, Jr.
Kevin K. Ohlemiller
14. GENETIC HEARING LOSS ASSOCIATED WITH
ENDOCRINE DISORDERS 571
5. SYNDROME DIAGNOSIS AND INVESTIGATION
IN THE HEARING-IMPAIRED PATIENT 85 Andrew Griffith and Helga V. Toriello
Raye L. Alford and Lorraine Potocki 15. GENETIC HEARING LOSS ASSOCIATED
WITH METABOLIC DISORDERS 599
6. GENETIC DIAGNOSIS AND GENE DISCOVERY
FOR HEARING LOSS USING MASSIVELY PARALLEL Sarah H. Elsea
SEQUENCING 91
16. GENETIC HEARING LOSS ASSOCIATED WITH
A. Eliot Shearer, Michael S. Hildebrand, INTEGUMENTARY DISORDERS 629
Christina M. Sloan, and Richard J.H. Smith
Helga V. Toriello
7. GENETIC HEARING LOSS WITH NO ASSOCIATED
17. GENETIC HEARING LOSS ASSOCIATED WITH
ABNORMALITIES 98
ORAL AND DENTAL DISORDERS 693
Shelley D. Smith
Helga V. Toriello
8. GENETIC HEARING LOSS ASSOCIATED WITH
18. GENETIC HEARING LOSS ASSOCIATED WITH
EXTERNAL EAR ABNORMALITIES 210
CHROMOSOME DISORDERS 700
Chad Haldeman-Englert
Cynthia C. Morton and
Anne B. Skvorak Giersch
9. GENETIC HEARING LOSS ASSOCIATED
WITH EYE DISORDERS 267
William Kimberling and Claes Moller Index 719

†
Robert J. Gorlin unfortunately passed away before this book was completed. He had done the majority of the work on this chapter, so his authorship is still
acknowledged.

xi
This page intentionally left blank
 CONTRIBUTORS

Raye L. Alford, PhD, FACMG Benjamin Kopecky, PhD

Baylor College of Medicine University of Iowa
Houston, TX Iowa City, IA
Holly H. Ardinger, MD Claes Moller, MD
Children’s Mercy Hospitals and Clinics Örebro University Hospital
Kansas City, MO Örebro, Sweden
Robert H. Ardinger, Jr., MD Cynthia C. Morton, PhD
Children’s Mercy Hospitals and Clinics Brigham and Women’s Hospital
Kansas City, MO Harvard Medical School
Boston, MA
Kathleen S. Arnos, PhD
Gallaudet University Martha A. Nance, MD
Washington, D.C. University of Minnesota
Golden Valley, MN
Sarah H. Elsea, PhD, FACMG
Baylor College of Medicine Kevin K. Ohlemiller, PhD
Houston, TX Washington University School of Medicine
Saint Louis, MO
Bernd Fritzsch, PhD
University of Iowa Arti Pandya, MD
Iowa City, IA Virginia Commonwealth University
Richmond, VA
Anne B. Skvorak Giersch, PhD
Brigham and Women’s Hospital Lorraine Potocki, MD
Harvard Medical School Baylor College of Medicine
Boston, MA Texas Children’s Hospital
Houston, TX
Andrew Griffith, MD, PhD
National Institute on Deafness and Other Communication Judy Savige, MB, BS, FRCP, FRACP, FRCPA, PhD, M Sc
Disorders, National Institutes of Health, Department of The University of Melbourne (Northern Health)
Health and Human Services The Northern Hospital
Rockville, MD Victoria, Australia
Chad Haldeman-Englert, MD, FACMG A. Eliot Shearer, MD, PhD
Wake Forest School of Medicine University of Iowa Carver College of Medicine
Winston-Salem, NC Iowa City, IA
Michael S. Hildebrand, PhD Christina M. Sloan, PhD
University of Iowa Carver College of Medicine Wartburg College
Iowa City, IA Waverly, IA
William Kimberling, PhD Richard J.H. Smith, MD, PhD
Boys Town National Research Hospital University of Iowa Carver College of Medicine
Omaha, NE Iowa City, IA

xiii
Shelley D. Smith, PhD Katherine O. Welch, MS, CGC
University of Nebraska Medical Center Gallaudet University
Omaha, NE Washington, DC
Helga V. Toriello, PhD
Spectrum Health Hospitals
Michigan State University College of Human Medicine
Grand Rapids, MI

xiv CONTRIBUTORS
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