The Encyclopedia of Genetic Disorders and Birth Defects, 3rd Edition (Facts on File Library of Health and Living)

705 Pages·2008·4.45 MB·English

by  James Wynbrandt, Deirdre A. Gaquin, Mark D. Ludman

THE ENCYCLOPEDIA OF
GENETIC DISORDERS
AND BIRTH DEFECTS
THIRD EDITION
James Wynbrandt
and
Mark D. Ludman, M.D., F.R.C.P.C
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The information presented in this book is provided for research purposes only
and is not intended to replace consultation with or diagnosis and treatment by
medical doctors or other qualified experts. Readers who may be experiencing or
witnessing a condition or disease described herein should seek medical attention
and not rely on the information found here as medical advice.
The Encyclopedia of Genetic Disorders and Birth Defects, Third Edition
Copyright © 1991, 2000, 2008 by James Wynbrandt
All rights reserved. No part of this book may be reproduced or utilized in any form or by any means,
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systems, without permission in writing from the publisher. For information contact:
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Library of Congress Cataloging-in-Publication Data
Wynbrandt, James
The encyclopedia of genetic disorders and birth defects / James Wynbrandt and Mark D. Ludman.—3rd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-8160-6396-3 (hc : alk. paper) 1. Genetic disorders—Encyclopedias. 2. Abnormalities, Human—
Encyclopedias. I. Ludman, Mark D. II. Title.
[DNLM: 1. Abnormalities—Encyclopedias—English. 2. Genetic Diseases, Inborn—Encyclopedias—
English. 3. Genetics, Medical—Encyclopedias—English. QS 13 W985e 2007]
RB155.5.W96 2007
616'.04203—dc22 2006100640
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CONTENTS
Preface iv
Acknowledgments v
Introduction vi
Entries A to Z 1
Appendixes 403
Bibliography 659
Index 64
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PREFACE
enetic disorders and birth defects comprise Entries for subjects and terminology important
Ga vast galaxy of anomalous conditions and to genetic disorders and congenital anomalies are
exert an extraordinary impact on the human also included. Entry titles used within the text of
population. Attempting even a partial catalog of other entries are in small capital letters the first
them is daunting, indeed. More than 4,300 “single time they appear, providing readers with numer-
gene” disorders have been reported and are esti- ous cross-references. However, we’ve attempted
mated to affect 1% of the population. The num- to make each entry stand alone, so that one can
ber of “multifactorial” disorders, those resulting achieve a general understanding of a given topic
from a combination of genes, is considered much without investigating additional entries. Resources
greater. If late onset disorders are included, 60% to assist those seeking more information are listed
of the population is thought to have a genetically in the appendixes. These are mostly private orga-
influenced disease. Additionally, significant con- nizations. Addresses, phone numbers, Web site
genital anomalies, apparently unrelated to genetic URLs and other contact information are found in
influence, number in the thousands and are seen the directory in the appendix. The appendix also
in approximately 2% to 3% of all live births. contains an extensive listing of state, regional and
We have included a little more than 1,000 federal government information resources. We
entries in this encyclopedia, selected on the basis urge readers to take advantage of these resources.
of the disorders’ incidence and clinical and his- Though entries were revised and updated through
torical importance. We describe the condition, its the final galley stage of this encyclopedia, rapid
prognosis, prevalence, mode of inheritance and the developments in the field of genetic and congenital
availability of carrier screening and prenatal diag- anomalies add new knowledge to our understand-
nosis. For whom the condition is named and addi- ing of this subject on an almost daily basis.
tional historical and anecdotal data are included
where applicable and available. When known, the James Wynbrandt
biochemical and molecular basis of the disorder is Mark D. Ludman, M.D.
also given.
iv
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ACKNOWLEDGMENTS
e could not have created this encyclopedia School of Medicine, the DuPont Institute, the
Wwithout the help of many people and orga- National Institute of Health, the National Center for
nizations. We wish to express our gratitude to Health Statistics, the National Center for Education
them all, citing a few by name. in Maternal and Child Health, the National Insti-
For their dedicated and tireless administrative tute of Child Health and Human Development, the
assistance, we are deeply grateful to Emily Alex- Administration on Developmental Disabilities, the
ander, Gina Caimi, Deborah Hayes and Eliza- Clearinghouse on the Handicapped and, of course,
beth Smith. For research and editorial assistance, the many support groups, associations and other
heartfelt thanks to Leslie Brennan, Serena Chin, organizations and individuals that were so gener-
Betsy Hanson, Michael Herring, Gunnar Mengers, ous with their time, resources and expertise.
Rachel Pettman, Elizabeth Prata, Jed Russell, We also wish to acknowledge all those physi-
Linda Smith, M.D., Don Sontup, Dina Stein, Diann cians and scientists who have contributed to the
Peterson Trolle, Gayle Turim and Brian Wade. For knowledge that we have endeavored to summarize
encouragement and guidance, Allan Schanske, and catalog here, as well as the individuals and
M.D., Rena Petrella, M.D., Ram Verma, M.D., and their families who have been touched by a genetic
Anita Lustenberger. We would also like to thank disorder or birth defect.
Kurt Hirschhorn, M.D., who first interested Dr. Dr. Ludman would also like to thank all those
Ludman in genetics and is responsible for the who taught him what he knows about genetics:
authors’ collaboration on this encyclopedia. For instructors throughout his training; students, who
their review and many helpful comments on the constantly challenge him to learn more; and col-
introductory essay, “A History of Human Genet- leagues at the Mount Sinai School of Medicine in
ics,” very special thanks to Victor A. McKusick, New York City and at the IWK Grace Health Cen-
M.D., and John M. Opitz, M.D. tre, Atlantic Research Centre and Dalhousie Uni-
Among the private and government organi- versity in Halifax, Nova Scotia.
zations and their staffs that provided unfailing Dr. Ludman expresses his appreciation to the
assistance, our gratitude to the March of Dimes Department of Human Genetics at Hadassah Med-
Birth Defects Foundation, the Children’s Defense ical Center in Jerusalem and the Department of
Fund, the American College of Obstetricians and Applied Human Nutrition at Mount Saint Vincent
Gynecologists, the Centers for Disease Control, the University in Halifax for providing research facili-
American Academy of Pediatrics, the library and ties during his sabbatical. It was at these institu-
rare book collection of the New York Academy of tions that much of the work for the encyclopedia’s
Medicine, Johns Hopkins University, Mount Sinai second edition was done. To his parents: Thanks
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vi The Encyclopedia of Genetic Disorders and Birth Defects
for instilling the love of knowledge. And espe- Benjamin Samuel, Aaron Joshua and Shayna
cially to his family for all the support they have Miriam. Dr. Ludman’s wife now understands all
given him throughout this project. He dedicates too well why books are often dedicated to authors’
this book to his wife, Batya, and to his children, spouses!
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INTRODUCTION
A HISTORY OF HUMAN GENETICS
ittle more than a century ago, in 1906, En glish gods. Astrological records from Babylon and
Lzoologist William Bateson suggested to the Nineveh dating to 2800 B.C. indicate a great famil-
scientific community that the study of heredity iarity with anomalous congenital conditions in
be named “genetics.” Millennia of misconception humans. Specific deformities were linked to spe-
preceded this christening, and the explosion of cific prophesies, heralding events from war to
knowledge that has occurred since continues at natural disasters such as an earthquake, as well
a remarkable pace. It is a science with a singular as peace or the favorable reign of a monarch. The
ability to influence life, both in the general and Greeks had their tales of cyclopes and stories of
individual sense, at its most profound level, a field hermaphrodites. In England in the Middle Ages,
with a promising future and a rich history. those who could not hear, and hence had not
Interest in the subject is as old as humankind learned to speak, were thought to be stupid and
and began with the realization that living things labeled “dumb.” And in the relatively recent past,
beget other living things in their own image and the curious have flocked to see “prodigies” (such
the observation of unique differences among indi- as Tom Thumb and Chang and Eng, the “Siamese”
viduals. Conditions arising from genetic aberra- twins), individuals whose physical abnormalities
tions have also been observed throughout human formed the basis of performing careers that often
history. For example, archaeologists have found brought them great fortune and renown.
remains of dwarfs dating to prehistoric times. No
doubt various legends and myths were created to
explain these variations, both normal and abnor- The Roots of Genetics
mal, explanations probably no more fanciful than What we now know as genetics has its roots in early
many that existed, even in scientific circles, from history, with the development of agriculture. Ani-
the beginning of recorded history until the dawn mal and plant breeding were employed in Egyptian
of the 20th century. times; farmers crossed their best stock, surmising
In a void without scientific understanding, the the offspring would also be superior. Babylonians
public historically has grappled with the causes are thought to have artificially cross-fertilized date
and consequences of these conditions and varia- palms. Stone carvings at least 4,000 years old from
tions on its own, resulting in a long tradition of Chaldea (near the Persian Gulf) describe differ-
fables and fallacies. ent pedigrees, showing the inheritance of specific
Babylonians regarded the birth of deformed traits of a horse’s mane. Jews recognized a familial
infants or stillborn fetuses as portents from the link in some diseases; according to the Tosafot, the
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viii The Encyclopedia of Genetic Disorders and Birth Defects
commentary on the law of the Talmud, a boy need neous assumptions based on classical Greek con-
not undergo circumcision if his mother had pre- cepts persisted through the Middle Ages. Among
viously given birth to two male infants who had them: The sex of a child is determined by the dom-
bled to death at circumcision. This is obviously an inator of the sexual act; characteristics of offspring
allusion to hemophilia, a hereditary disorder seen arise from the heat of the womb or which testis the
almost exclusively in males, but whose pedigree sperm came from; sperm is secreted from all parts
pattern was not recognized by the scientific com- of the body during intercourse and responsible
munity until the 1800s. for reproducing that part of the body from which
It was likewise recognized that children often it was secreted. In the 1600s, the concept of the
appeared to resemble their parents and that cer- “manikin” was popular: Each sperm contained a
tain traits ran in families. Around 500 B.C., small but complete “manikin,” which would sim-
Pythagoras, the philosopher and mathematician, ply grow larger in the womb, rather than develop
theorized that human life originated from a blend as a plant from a seed. In the 1700s, a theory of
of male and female fluids, or semens, that came heredity popularized by French naturalist George-
from within the body. Two centuries later, Aristo- Louis Leclerc, comte de Buffon postulated that
tle, who believed males were primarily responsible the male determined bodily extremities (head,
for passing on hereditary characteristics, proposed tail, limbs) while the female was responsible for
that the semens were purified elements of blood, a internal constituents and overall size and shape.
belief that lingers today in phrases such as “blood A belief that persisted beyond that century was
relative” and “royal blood.” Hippocrates, the father that the “essence” from each vital organ of the
of medicine (ca. 460–377 B.C.), had his own ideas parents’ bodies somehow blended to create a new
about these fluids: “The semen is produced by the individual. However, foreshadowings of modern
whole body, healthy by healthy parts, sick by sick concepts of heredity began to appear. In the mid-
parts. Hence, when as a rule, baldheaded beget 1600s, Dutch scientist Regnier de Graaf advanced
baldheaded, blue eyed beget blue eyed, and squint- the idea of a new being arising from the union of
ing, squinting.” He had the mode of transmission sperm and egg. (The question of whether the pri-
wrong, but he clearly recognized the genetic nature mary component of heredity transmission was the
of certain traits and disorders, as is further noted sperm or the egg led to a lively dispute between the
in his comments about epilepsy, the “divine” afflic- so-called “ovists” and “spermatists.”)
tion (so called because those afflicted were said to During the 1700s, pedigrees, the patterns
have been blessed by the gods): “But this disease whereby traits are transmitted from generation
seems to me to be no more divine than others . . . to generation, were recognized for the first time.
Its origin is hereditary like that of other diseases (Members of the Hapsburgs, the ruling family of
. . . What is to hinder it from happening that where the Austrian Empire, were known in the Middle
the father and mother were subject to this disease, Ages for a characteristic “Hapsburg nose” and jut-
certain of their offspring should be affected also?” ting chin seen in portraits extending over several
The Institutes of Manu in India during the first centuries.) In 1751, French naturalist Pierre-Louis
centuries of the Common Era proposed an agricul- Moreau de Maupertuis invoked “elementary par-
tural model of heredity: Males provided the seed, ticles” as a transmission agent to explain a family
while females provided the field in which the seed in which several generations exhibited the trait of
was planted and grew. polydactyly (having more than the normal num-
Despite these pioneering efforts, the nature of ber of fingers and/or toes). In Système de la Nature,
the connection between the parent and offspring, he also suggested that mutations might account for
its method of transmission, how deformities arose, the diversity of life.
how hereditary patterns emerged or how they Botanists became interested in plant breeding,
could remain hidden through generations was leading to horticultural experiments that laid the
completely unknown. For centuries it remained a groundwork for modern genetics. When new spe-
riddle, referred to as “the mysterious force.” Erro- cies of plants appeared, as they did periodically,
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Introduction ix
efforts were made to explain their occurrence. In concluded the changes were the result of random
1760, Joseph Gottlieb Kolreuter created the first variations. If the variation was beneficial, those
experimentally produced plant hybrid (the off- possessing it were more likely to survive and multi-
spring of two different species), by mixing two ply, a theory he called “natural selection.” Darwin
species of the tobacco plant. This in turn helped published his interpretation of these observations
generate extensive studies of the function of pol- after his attention was brought to a manuscript by
len. He also proposed, as had Maupertuis, that both Alfred Russell Wallace, who was about to publish
parents contributed an equal hereditary element to a paper with similar conclusions based on observa-
their offspring. Yet, other than botanical studies, tions in the Malaysian islands. Darwin’s theories,
the scientific community showed little interest in further delineated in The Descent of Man (1871),
questions of genetics and heredity, an attitude that also addressed common ancestry among species,
changed markedly in the 19th century, as a spirit a concept often misinterpreted as man’s having
of inquiry and innovative technologies spread. descended from apes. To this day, in the West-
In 1814, Joseph Adams published “A Treatise ern world, Darwin’s theories of evolution are not
on the Supposed Hereditary Property of Disease,” universally accepted, primarily by those who find
a remarkably prescient work in which he indi- them incompatible with biblical accounts of the
cated an appreciation for many of the hallmarks origin of life.
of hereditary theory. He distinguished between As science became more sophisticated in its out-
recessive and dominant conditions, noted heredi- look on genetics and heredity, so did the public.
tary predisposition in some disorders and the role The hereditary nature of some disorders was now
of environmental influence in their development, accepted. One of the characters in Nathaniel Haw-
and surmised that higher rates of familial dis- thorne’s The House of the Seven Gables, published in
eases found in isolated populations could be due 1851, suffered from a disease (now speculated as
to inbreeding. He even invoked the concept of new being hereditary angioedema) that Hawthorne
mutations, by stating that the reproductive ability described as a fatal condition whose “mode of
of many patients with hereditary conditions would death has been an idiosyncrasy with this family,
eventually disappear were it not for their sponta- for generations past.” Hemophilia was also known
neous appearance in healthy families. in New England to have a hereditary component.
A familial link in color blindness had been recog-
nized by the end of the 18th century.
Darwin and Mendel
It was also during this time that Gregor Johann
During the mid-19th century, attention shifted Mendel (1822–84) was conducting experiments
from different species to variations within a given with garden peas. Mendel, an Austrian, was a
species (population groups) and the question of monk in Brünn (now Brno), Moravia (now a part
why various populations of a species were not all of the Czech Republic). Beginning his experiments
alike. The major catalyst for the shift was Charles in 1856, he noticed that pea plants had vary-
Darwin’s (1809–82) monumental On the Origin of ing traits; some unripe pods were yellow, others
Species by Means of Natural Selection (1859), which green; some varieties were tall, while others were
created an intense interest in the mechanics of dwarfed. The position of the flowers, whether clus-
evolution. Darwin was already well respected for tered at the top or distributed along the stem, also
his first book, The Zoology of the Voyage of the Bea- varied, as did the physical appearance of the peas
gle (1840), an account of his five-year voyage on themselves, being either smooth or wrinkled.
H.M.S. Beagle, on which he sailed as an unpaid Using hybrid garden pea plants, Mendel’s goal
naturalist. At one stop, the Galápagos Islands, 15 was to study the transmission of characteristics to
small rocky outcroppings straddling the equator their offspring, and the statistical relation of their
some 700 miles west of South America, Darwin subsequently appearing traits. Mendel had studied
noted that species of birds that had migrated to physics and mathematics, and he carefully recorded
different islands had evolved slight differences. He and attempted to explain his observations. During
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