The Genetics of Cardiovascular Disease PDF
Preview The Genetics of Cardiovascular Disease
THE GENETICS OF CARDIOVASCULAR DISEASE THE GENETICS OF CARDIOV ASCULAR DISEASE edited by Mary Ella Mascia Pierpont Department of Pediatrics and Institute of Human Genetics University of Minnesota James H. Moller Department of Pediatrics University of Minnesota "~ Martinus Nijhoff Publishing a member of the Kluwer Academic Publishers Group BOSTON DORDRECHT LANCASTER DISTRIBUTORS for the United States and Canada: Kluwer Academic Publishers, 101 Philip Drive, Norwell, MA 02061 for the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited, Falcon House, Queen Square, Lancaster LA1 1RN, UK for all other countries: Kluwer Academic Publishers Group, Distribution Centre, P.O. Box 322, 3300 AH Dordrecht, The Netherlands Library of Congress Cataloging-in-Publication Data Genetics of cardiovascular disease. Includes index. 1. Heart - Abnormalities. 2. Cardiovascular system - Diseases - Genetic aspects. 3. Medical genetics. I. Pierpont, Mary Ella Mascia. II. Moller, James H., 1933- . [DNLM: 1. Cardiovascular Diseases - familial & genetic. 2. Heart Defects, Congenital. WG 220 G3282] RC687.G43 1986 616.1'042 85-32038 ISBN-13: 978-1-4612-9419-1 e-ISBN-13: 978-1-4613-2305-1 DOl: 10.1007/978-1-4613-2305-1 © 1987 by Martinus Nijhoff Publishing, Boston. Softcover reprint of the Hardcover 1s t edition 1987 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, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publishers, Martinus NijhoffPublishing, 101 Philip Drive, Norwell, MA 02061 USA. CONTENTS Contributing Authors VI Acknowledgments Vlll Preface IX 1. Mechanisms in the Pathogenesis of 10. Abnormalities of Intermediary Congenital Cardiac Malformations 3 Metabolism 193 Edward B. Clark Mary Ella M. Pierpont Marjorie E. Tripp 2. Congenital Cardiac Malformations 13 11. Storage Disorders 215 Mary Ella M. Pierpont James H. Moller Reed E. Pyeritz 3. T eratogens 25 12. Neuromuscular Disorders 241 Tomas Pexieder Fred A. Ziter Frank H. Tyler 4. Chromosomal Abnormalities 69 13. Heritable Disorders of Connective Mary Ella M. Pierpont Robert J. Gorlin Tissue 265 James H. Moller Reed E. Pyeritz 5. Congenital Cardiac Malformations and 14. Blood Pressure in Children 305 Syndromes 95 Trudy L. Burns Catherine A. Neill Ronald M. Lauer 6. Congenital Cardiac Anomalies and 15. Hematologic Disease 319 Gastrointestinal Malformations 113 Mary Allen Engle Amnon Rosenthal Kathryn H. Ehlers John E. O'Loughlin Patricia Giardina 7. Disturbances of Cardiac Rhythm 127 Margaret Hilgartner Ann Dunnigan D. Woodrow Benson,Jr. 16. Vascular Abnormalities 339 James H. Moller 8. ldiopathic Cardiomyopathies 143 Richard Emanuel 17. Abnormal Tissue Growth 349 ROT/aid Withers Russell V. Lucas,Jr. 9. Genetic Dyslipoproteinemias Associated Index 367 with Coronary Atherosclerosis 161 Julia Lee Trudy L. Burns V CONTRIBUTING AUTHORS D. Woodrow Benson,Jr., M.D., Ph.D. National Heart Hospital Associate Professor of Pediatrics Sen. Physician, Cardiac Department Department of Pediatrics The Middlesex Hospital University of Minnesota Hospital and, Variety London, England Club Children's Hospital Mary Allen Engle, M.D. Box 94 Stavros S. Niarchos Professor of Pediatric 420 Delaware Street, S.E. Cardiology Minneapolis, MN 55455 Division of Pediatric Cardiology Trudy L. Burns, Ph.D. Department of Pediatrics Ass~stant Professor The New York Hospital-Cornell University Department of Preventive Medicine and Medical College Environmental Health New York, NY 10021 University of Iowa Hospitals and Clinics Patricia Giardina, M.D. Iowa City, IA 52242 Associate Professor of Clinics Pediatrics Edward B. Clark, M.D. Director of Thalassemia Clinic Associate Professor of Pediatrics and Division of Pediatric Hematology/Oncology Cardiologist Department of Pediatrics Division of Pediatric Cardiology The N ew York Hospital-Cornell University The Johns Hopkins University School of Medical College Medicine New York, NY 10021 Brady 516 Robert]. Gorlin, D.D.S., M.S. 600 N. Wolfe Street Regents Professor and Chairman Baltimore, MD 21205 Department of Oral Pathology and Genetics Ann Dunnigan, M.D. School of Dentistry Assistant Professor of Pediatrics University of Minnesota Hospital Department of Pediatrics Box 80 University of Minnesota Hospital and Variety 420 Delaware Street, S.E. Club Children's Hospital Minneapolis, MN 55455 Box 94 Margaret Hilgartner, M.D. 420 Delaware Street, S.E. Professor of Pediatrics Minneapolis, MN 55455 Director of Division of Pediatric Hematology/ Kathryn H. Ehlers, M.D. Oncology Professor of Pediatrics Department of Pediatrics Division of Pediatric Cardiology The New York Hospital-Cornell University Department of Pediatrics Medical College The New York Hospital-Cornell University New York, NY 10021 Medical College Ronald M. Lauer, M.D. New York, NY 10021 Professor Richard Emanuel, M.A., D.M., F.R.C.P. Director, Division of Pediatric Cardiology Lecturer, Cardiothoracic Institute Departments of Pediatrics and Preventive London University Medicine Physician University of Iowa Hospitals and Clinics VI Iowa City, IA 52242 Assistant Professor of Pediatrics and Genetics Department of Pediatrics . Julia Lee, M.D. Institute of Human Genetics Associate in Pediatrics University of Minnesota Hospital and Variety Division of Pediatric Cardiology Club Children's Hospital Department of Pediatrics Box 94 University of Iowa Hospitals and Clinics 420 Delaware Street, S.E. Iowa City, IA 52242 Minneapolis, MN 55455 Russell V. Lucas,Jr., M.D. Reed E. Pyeritz, M.D., Ph.1?: . . Professor of Pediatrics Associate Professor of Medlcme and Pedlatncs Department of Pediatrics Director of Clinical Services University of Minnesota Hospital and Variety Division of Medical Genetics Club Children's Hospital The Johns Hopkins University School of Box 94 Medicine 420 Delaware Street, S.E. Baltimore, MD 21205 Minneapolis, MN 55455 Amnon Rosenthal, M.D. James H. Moller, M.D. Professor of Pediatrics and Communicable Professor of Pediatrics Diseases Dwan Professor in Education in Pediatric University of Michigan . Cardiology C.S. Mott Children's Hospital Department of Pediatrics. . Ann Arbor, MI 48109 University of Minnesota Hospital and Vanety Club Children's Hospital Marjorie Ellen Tripp, M.~. . Box 288 Assistant Professor of Pedlatncs 420 Delaware Street, S.E. Department of Pediatrics . Minneapolis, MN 55455 University of Chicago Hospitals Catherine A. Neill, M.D. Wyler Children's Hospital Associate Professor of Pediatrics and 5841 South Maryland Avenue Cardiologist Box 132 Helen B. Taussig Heart Center Chicago, IL 60637 The Johns Hopkins University School of Frank H. Tyler, M.D. Medicine Professor of Medicine Brady 516 Department of Medicine . . 600 North Wolfe Street University of Utah School of Medlcme Baltimore, MD 21205 50 North Medical Drive John E. O'Loughlin, M.I?. .. Salt Lake City, UT 84132 Associate Professor of ClImcal Pedlatncs Ronald Withers, M.Sc., A.K.C. Division of Pediatric Cardiology Hon. Lecturer, Cardiothoracic Institute Department of Pediatrics London University The New York Hospital-Cornell University Sen. Lecturer in Human Genetics Medical College Department of Anatomy and Biology as New York, NY 10021 Applied to Medici~e . Tomas Pexieder, M.D. The Middlesex Hospital Medical School Associate Professor London, England Institute of Histology and Embryology Fred A. Ziter, M.D. Faculty of Medicine Professor of Neurology and Pediatrics University of Lausanne Rue du Dugnon 9 Division of Pediatric Neurology Ch-1011 Lausanne-CHUV Departments of Neurology and P~d~atrics Switzerland University of Utah School of Medlcme 50 North Medical Drive Mary Ella Mascia Pierpont, M.D., Ph.D. Salt Lake City, UT 84132 Vll ACKNOWLEDGMENTS The editors would like to acknowledge our Family Fund and the March of Dimes-Birth colleagues at the University of Minnesota in the Defects Foundation for their support. The ex pediatric and adult divisions of cardiology and pert assistance of Linda Boche and Mary Jo genetics. Their stimulation, interest, and coop Antinozzi in the preparation of the manuscripts eration has been invaluable in planning and is gratefully acknowledged. assembling this book. We thank the Dwan Vlll PREFACE Over the past 25 years, the growing impor cardiovascular. We hope that by having this tance of genetic factors in the basic understand compilation of cardiovascular diseases in one ing of human cardiovascular disease has become source, it will be of value to all who are involved apparent. Prior to this time, there was an era in the care of patients with cardiovascular dis when cardiovascular disease was first viewed at ease or their families. the diagnostic level followed by an era when The first six chapters of this book delineate cardiovascular disease was viewed at a treatment conditions related to congenital cardiac mal level. The first era occurred at the turn of the formations. Their etiology is not precisely century with the first clinical recognition of known, so we have included chapters that dis symptoms and patterns for diagnosis of car cuss many aspects of congenital cardiac mal diovascular diseases. The development of formations. The first chapter provides discus diagnostic methodology, such as radiographic sion of mechanisms of maldevelopment of the studies and electrocardiography, led to marked heart. We believe that these mechanisms pro changes in our understanding of cardiovascular vide a basis for understanding the genetic and disease. This era was followed by improved environmental factors which operate to produce methods of medical treatment, introduction congenital cardiac malformations. of medication such as antibiotics, and more Chapter 2 describes the occurrence of con sophisticated surgical techniques. genital cardiac malformations in families and Now we are in an era in which efforts are provides the current state of knowledge about being made to prevent cardiovascular disease, recurrence risks for the major congenital cardiac prevention through methods such as risk factor malformations. The third chapter provides evi identification for atherosclerosis, prophylactic dence that congenital cardiac malformations are antibiotics, and appropriate diagnosis. The pre an important component of syndromes asso vention of cardiovascular disease has its basis ciated with chromosomal aberrations. While in genetic counseling of the affected individual, some of these chromosomal conditions, such as of the family, of the physician, and of all Down syndrome, or Turner syndrome, are well allied health professionals. It is now possible to known, the cardiac and other phenotypic fea provide genetic counseling about many car tures of more than 60 other chromosomal diovascular diseases because of the development aberrations are described for handy reference. of more sophisticated methods of detection of Knowledge of the presence and type of chromo genetic disease, methods such as cytogenetics somal abnormality and cardiac malformation and chromosomal banding, biochemical genetic provides valuable information for those who definition of enzyme activity, and molecular care for these children and for those who coun genetic techniques to identify the causal factors sel the family. at the gene level. With these tools, the various Over the past 20 years, we have learned more forms of cardiovascular disease can be studied about teratogenetic mechanisms and their rela and many diseases whose cause is presently tionship to the heart. We have included an unknown will be recognized to have a genetic extensive chapter (chapter 4) on teratogens and origin or at least a genetic component. the heart. This chapter adds significantly to our In this book, we have attempted to provide a understanding of the mechanisms of mal textbook source of most cardiovascular condi development of the heart, although these mal tions and their genetic basis. Some of these formations are largely due to environmental diseases are primarily cardiac, some involve agents and, to a lesser degree, genetic suscepti other organs but have a major cardiac compo bility . We believe this chapter on teratogens will nent, and some involve primarily other organ be useful for providing counseling to families systems but have a minor component which is when situations of fetal exposure have occurred, lX x PREFACE and that this chapter will be a medical-legal Heritable diseases of connective tissue, which reference in the future. include the Marfan syndrome, are many and Congenital cardiac malformations occur in varied. This group of diseases primarily affects several multisystem diseases associated with a the cardiac valves and major blood vessels. single gene abnormality. The clinical features Clinical recognition of the patient with this type and genetic implications of 14 syndromes are of disorder will also lead to recognition of the discussed in chapter 5. Congenital cardiac mal specific patterns of cardiovascular abnormal formations may coexist with anomalies of other ities. organ systems. We have the greatest knowledge Hematologic conditions can have a profound about the major malformations of the gastroin affect on the function of the heart. Diseases such testinal tract, since they are easily identified and as thalassemia and sickle cell anemia have pro very few escape detection. Chapter 6 provides found cardiovascular effects, not only through information regarding the coexistent malforma the creation of anemia but in the development tion of these two organ systems. of cardiac dysfunction. The application of With the recent development of electrophys molecular genetic techniques to the study of iologic techniques for diagnosis, cardiologists thalassemia and hemoglobinopathies represents have developed the ability to define and classify a significant advance in our understanding of cardiac rhythm disturbances in a more precise these diseases. Furthermore, our ability to pro manner. This more detailed recognition will vide accurate diagnosis has also been significant allow us to understand better the genetic aspects ly improved. of important and occasionally life-threatening Systemic hypertension (chapter 14) is a wide arrhythmias of the heart. ly prevalent disease in the Western world and a Our understanding of cardiac muscle disease major cardiovascular risk factor. Through satis remains at an elementary level. Many diseases factory genetic techniques, many aspects of which result in a cardiomyopathy or cardiac hypertension are being evaluated, and further muscle dysfunction have a clear genetic basis development of this area may await the develop (chapter 10, chapter 11). Yet there are many ~ent of rapid molecular genetic diagnostic tech families in which cardiomyopathy occurs in mques. numerous relatives and a known biochemical The last two chapters of the book provide mechanism has not been defined. Chapter 8 information regarding unusual conditions summarizes the present state of knowledge of which primarily affect blood vessels and abnor idiopathic cardiomyopathies. malities of tissue growth. There are a large There is an enormous varfety of biochemi number of unusual conditions which primarily cal diseases which are clearly associated affect blood capillaries, arteries, veins, and lym with specific laboratory and clinical findings in phatic vessels. These conditions, such as Milroy the cardiovascular system. These metabolic disease and familial primary pulmonary hyper abnormalities may occur in lipid metabolism tension, are discussed together in one chapter (chapter 9), intermediary metabolism (chapter for the first time (chapter 16). 10), and a wide variety of storage disease (chap The final chapter of this book provides in ter 11). Our understanding of the biochemistry formation regarding diseases with abnormal of these diseases is rapidly enlarging, and it is tissue growth (tuberous sclerosis, neuro clea~ that many gains will be made with each fibromatosis). This is particularly pertinent passmg year. since neurofibromatosis is a very common gene There are many forms of acquired cardio tic condition. vascular disease. Many acquired cardiac diseases In all of these chapters, the clinical features develop as a component of other conditions are described and the cardiovascular manifesta which primarily affect other organ systems, tions presented. Furthermore, the use of prena such as neuromuscular conditions with cardiac tal diagnostic techniques is discussed, and it is involvement. In chapter 12, we emphasize the clear that the use of new molecular genetic potential relationship between abnormalities of techniques is an important breakthrough in skeletal muscle and cardiac muscles. For exam the understanding of many human diseases; We ple, it is already well known that many indi are presently at the threshold of understanding viduals with major features of cardiomyopathy of the molecular biology of the heart. This book may also have minor evidence of skeletal muscle is intended as a source book, and periodic weakness. revision is planned. THE GENETICS OF CARDIOVASCULAR DISEASE
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