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The Practical Guide to the Genetic Family History The Practical Guide to the Genetic Family History. Robin L. Bennett Copyright © 1999 Wiley-Liss, Inc. ISBNs: 0-471-25154-2 (Paper); 0-471-22391-3 (Electronic) The Practical Guide to the Genetic Family History The Practical Guide to the Genetic Family History Robin L. Bennett A JOHN WILEY & SONS, INC., PUBLICATION New York ț Chichester ț Weinheim ț Brisbane ț Singapore ț Toronto Designations used by companies to distinguish their products are often claimed as trademarks. In all instances where John Wiley & Sons, Inc., is aware of a claim, the product names appear in initial capital or ALL CAPITAL LETTERS. Readers, however, should contact the appropriate companies for more complete information regarding trademarks and registration. Copyright © 1999 by Wiley-Liss, Inc. 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, electronic or mechanical, including uploading, downloading, printing, decompiling, recording or otherwise, except as permitted under Sections 107 or 108 of the 1976 United States Copyright Act, without the prior written permission of the Publisher. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158-0012, (212) 850-6011, fax (212) 850-6008, E-Mail: PERMREQ @ WILEY.COM. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold with the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional person should be sought. ISBN 0-471-22391-3 This title is also available in print as ISBN 0-471-25154-2. For more information about Wiley products, visit our web site at www.Wiley.com. To Scott, Mom, and Mr. Tougaw: thanks for believing in me CONTENTS Illustrations and Tables ix Foreword xiii Preface xv 1. The Language of the Pedigree 1 2. Practical Inheritance 13 3. Getting to the Roots: Recording the Family Tree 38 4. Directed Medical-Genetic Family History Queries: 68 Separating the Trees from the Forest 4.1 The Approach / 68 4.2 Physical Birth Anomalies and Variants / 71 4.3 Deafness/Hearing Loss / 83 4.4 Vision Impairment / 88 4.5 Mental Retardation / 92 4.6 Autism / 99 4.7 Neurological and Neuromuscular Disorders / 100 4.8 Seizures / 102 4.9 Dementia / 104 4.10 Mental Illness / 106 4.11 Disorders Involving the Cardiac System / 107 4.12 Chronic Respiratory Disease / 111 4.13 Renal Disorders / 112 4.14 Skeletal Anomalies and Disorders of Short Stature / 115 vii viii CONTENTS 4.15 Diabetes / 119 4.16 Reproductive Failure, Infertility, and Multiple Miscarriages / 120 4.17 Sudden Infant Death Syndrome / 123 5. Using a Pedigree to Recognize Individuals with an Increased 129 Susceptibility to Cancer 6. Medical Verification of a Family History 145 7. The Challenge of Family History and Adoption 154 8. The Pedigree and Assisted Reproductive Technologies 160 9. Making a Referral for Genetic Services: 166 Where to Turn and What to Expect 10. Pedigree Predicaments 173 Glossary 181 Appendices A.1 Handy Reference Tables of Pedigree Nomenclature 191 A.2 Sample Clinical Pedigree Form 194 A.3 Sample Genetic Screening Form for Familial Cancer Risk Assessment 196 A.4 Sample Adoption Medical-Family History Form 199 A.5 The Genetics Library 212 A.6 Genetics in Practice: Five Case Studies 225 Index 239 Illustrations and Tables Figure 1.1 A sippschaftstafel. Figure 1.2 A hypothetical pedigree representative of a family with von Hippel–Lindau syndrome. Figure 1.3 The Family Tree, quilt. Figure 2.1 Representative pedigree of autosomal dominant (AD) inheritance. Figure 2.2 Representative pedigree of autosomal recessive (AR) inheritance. Figure 2.3 Representative pedigree of an X-linked recessive condition (XLR). Figure 2.4 Pedigree suggestive of an X-linked mutation that is lethal in males. Figure 2.5 Representative pedigree of X-linked dominant inheritance. Figure 2.6 Representative pedigree of multifactorial inheritance. Figure 2.7 Representative pedigree of an inherited chromosome translocation. Figure 2.8 Representative pedigree of mitochondrial inheritance. Figure 3.1 Pedigree line definitions. Figure 3.2 Numbering generations and individuals on a pedigree. Figure 3.3 The pedigree framework for denoting a relative’s relationship to the proband. Figure 3.4 The most common pedigree symbols. Figure 3.5 Pedigree symbols related to pregnancy. Figure 3.6 A pedigree of actress Elizabeth Taylor demonstrating how to illustrate multiple marriage partners, stepchildren, and half siblings. Figure 3.7 Pedigree symbolization of adoption. Figure 3.8 Hypothetical pedigree demonstrating how to shade affected individuals when more than one condition is segregating in a family. Figure 3.9 How to document results of medical evaluations and genetic testing on a pedigree. Figure 3.10 Symbolization of first cousins, first cousins once removed, and second cousins. Figure 3.11 A pedigree of first cousins, Charles Darwin and his wife Emma Wedgwood Darwin. ix x ILLUSTRATIONS AND TABLES Figure 5.1 The empirical risk to develop breast cancer based on the age of onset of breast cancer in a mother and maternal aunt. Figure 6.1 A release form for obtaining medical records on a relative. Figure 8.1 Pedigree symbolization of assisted reproductive technologies. Figure 10.1 A pedigree of the Wedgwood–Darwin–Galton family. Table 1.1 The Pedigree As a Valuable Tool in Patient Education Table 1.2 Common Patient Misconceptions about Inheritance Table 2.1 Pedigree Clues for Distinguishing the Primary Patterns of Human Inheritance Table 2.2 Examples of Autosomal Dominant Conditions Table 2.3 Examples of Autosomal Recessive Conditions Table 2.4 Examples of X-Linked Conditions Table 2.5 Medical and Family History Features Suggestive of Conditions Caused by Mitochondrial Mutations Table 2.7 Examples of Conditions with Mitochondrial Inheritance Table 3.1 Essential Information to Record on Family Members in a Pedigree Table 3.2 Human Teratogens: Proven, Possible, and Unlikely Table 3.3 Genetic Disorders That Have a High Incidence in Certain Ethnic Groups Table 3.4 Possible Explanations for a Seemingly Unremarkable Family History Table 4.1 The Red Flags in Medical-Family History Table 4.2 Examples of Major Congenital Anomalies Table 4.3 Examples of Minor Physical Differences That Can Be Within Normal Variation or a Feature of a Syndrome (Inherited or Environmental) Table 4.4 Medical-Family History Questions for Congenital Anomalies Table 4.5 Common Cardiac Teratogens Table 4.6 Minimal Medical-Family History Information for an Abnormal Fetal Ultrasound Table 4.7 Medical-Family History Questions for Deafness/Hearing Loss Table 4.8 The Medical-Family History Approach to Visual Loss Table 4.9 Examples of Hereditary and Environmental Syndromes Associated with Early-Onset Cataracts Table 4.10 Medical-Family History Queries for Cataracts Table 4.11 Features Suggestive of a Metabolic Genetic Disorder Table 4.12 Features to Document in the Medical-Family History When a Family Member Has Mental Retardation Table 4.13 Medical-Family History Questions for Autism Table 4.14 Medical-Family History for Neurological and Neuromuscular Disorders Table 4.15 Medical-Family History Questions for a Seizure Disorder Table 4.16 Inherited Disorders Associated with Adult-Onset Dementia Table 4.17 Medical-Family History Questions for Dementia Table 4.18 Genetic Disorders That May Present with Psychiatric or Severe Behavioral Abnormalities ILLUSTRATIONS AND TABLES xi Table 4.19 Medical-Family History Queries for Mental Illness Table 4.20 Medical-Family History Questions for Cardiac Disease Table 4.21 Medical-Family History Questions for Chronic Respiratory Disease Table 4.22 Medical-Family History Questions for Renal Disorders Table 4.23 Common Causes of Proportionate Short Stature Table 4.24 Medical-Family History Questions for Short Stature or Skeletal Dysplasias Table 4.25 Medical-Family History Questions for Diabetes Mellitus Table 4.26 Genetic Causes of Male Infertility Where Infertility May Be a Presenting Clinical Feature Table 4.27 Medical-Family History Questions Related to Male Infertility Table 5.1 Medical-Family History Features Suggestive of a Hereditary Cancer Syndrome or a Site-specific Cancer Susceptibility Table 5.2 Medical-Family History Queries for Cancer Table 5.3 Known Autosomal Dominant Cancer Predisposition Syndromes and Their Gene Locations Table 5.4a Autosomal Dominant Cancer Syndromes and Their Associations with Benign Tumors and Neoplasms Table 5.4b Autosomal Dominant Cancer Syndromes (Continued) Table 5.5 Selected Genetic Syndromes Associated with Neoplasms and Their Inheritance Patterns Table 5.6 Preferential Metastatic Sites of Some Human Tumors Table 5.7 Life-style and Occupational Risk Factors for Cancer Table 6.1 Sample Letter to Request a Family Member’s Medical Records Table 8.1 Comparisons of How Gamete Donation Can Reduce the Risk for a Genetic Disease, Based on Inheritance Patterns and the Affected Status of the Partner Table 9.1 Common Medical Conditions with Onset in Adulthood for Which Genetic Susceptibility Testing is Potentially Available Table 10.1 Unique Issues in Family Studies Foreword Robin Bennett’s book is a superb introduction to clinical approaches in medical genetics. Centered on the most traditional diagnostic tool in clinical genetics—the family history—she presents a well-balanced discussion of all of its aspects including the many applications for diagnosis of genetic disease. The book is based on extensive personal experience and provides much practical and useful information. But there is much more! The book’s contents reflect the most recent genetic developments in all medical specialties, not just pediatric and obstetric aspects. Thus the rapidly expanding knowledge in cancer genetics is covered, as are various genetic considerations about assisted reproduction for women as well as for men (intracytoplasmic sperm injection).
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