Cleft lip and palate : from origin to treatment

547 Pages·2002·49.565 MB·English

by  Wyszynski, Diego F

Cleft Lip and Palate
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CLEFT LIP
AND PALATE
From Origin to Treatment
Edited by
DIEGO F. WYSZYNSKI
Genetics Program
Department of Medicine
Boston University School of Medicine
and
Department of Epidemiology
Boston University School of Public Health
Boston, Massachusetts
OXPORD
UNIVERSITY PRESS
2002
OXFORD
UNIVERSITY PRESS
Oxford New York
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Copyright © 2002 by Oxford University Press, Inc.
Published by Oxford University Press, Inc.
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Oxford is a registered trademark of Oxford University Press
All rights reserved. No part of this publication may be reproduced,
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Library of Congress Cataloging-in-Publication Data
Cleft lip and palate : from origin to treatment / edited by Diego F. Wyszynski.
p. ; cm.
Includes bibliographical references and index.
ISBN 0-19-513906-2
1. Cleft lip. 2. Cleft palate. 3. Cleft lip—Surgery. 4. Cleft palate—Surgery. I.
Wyszynski, Diego F.
[DNLM: 1. Cleft lip. 2. Cleft Palate. WV 440 C62152 2002]
RD524.C525 2002
617.5'22—dc21 2001133031
246897531
Printed in Hong Kong
on acid-free paper
Foreword
This book is a testament to the remarkable growth of ronmental harm; the causes of malformations were, by
knowledge of oral clefts in the past three-quarters of a exclusion, genetic. Now the pendulum had shifted, and
century. In a foreword, it seems appropriate to con- the causes of malformations were increasingly seen as
sider the early studies of causation that were the ori- environmental. The pendulum began to shift back to
gins of the panorama of knowledge that this volume an intermediate position, not one or the other but both,
presents. The following is a very personal view of some when it was shown, at McGill, that the same terato-
of the events that were milestones in oral cleft history gen can cause very different frequencies of a malfor-
and will undoubtedly have omissions, which are quite mation on different genetic backgrounds. Genes influ-
unintentional. enced the embryo's response to teratogens, and
When I was in graduate school in the early 1940s, maternal as well as embryonic genes could be involved.
knowledge of causation had not progressed much be- Cortisone and CP in mice, the first example, was soon
yond the old wive's tales that mothers would tell me followed by others, and from these beginnings there de-
about being frightened by a wolf (from geule-de-loup) veloped the field of teratogenics.
or drawing the knife toward themselves while cutting Studies of how the mouse palate closed and how clo-
bread. sure was delayed by cortisone led to the concept of CP
In the late 1930s, Sheldon Read, at McGill Univer- as a multifactorial/threshold trait. A continuous distri-
sity, began to explore the genetics of cleft lip (CL) in bution of liability (time of shelf closure) was separated
an ancestor of the A/Jax mouse line, and the Danish into discontinuous portions, affected and unaffected,
plastic surgeon Paul Fogh-Anderson, for his M.D. the- by a threshold (the last point in time that closure was
sis, was collecting the monumental series of family his- possible). Specific genetic and environmental factors
tories of children with cleft lip and palate (CLP) and were identified that altered CP frequency, by affecting
cleft palate (CP) that provided the first reliable esti- either the position of the distribution or the position of
mates of recurrence risks for use in genetic counseling. the threshold.
In the late 1940s, Ted Ingalls, a Boston pediatrician, In the meantime, the multifactorial threshold concept
became convinced that maternal hypoxia was terato- was being independently developed by Cedric Carter,
genic. He had seen a woman who had had a motor ac- in London. He inferred it from a peculiarity in the re-
cident on the 52nd day of her pregnancy, had bled, and currence risks for hypertrophic pyloric stenosis. Why
had had a child with Down syndrome. He reasoned was the recurrence risk higher for the near relatives of
that since all of the developmental processes that went affected females, when the frequency of the disorder is
wrong in Down syndrome happened on that day, ma- lower in females? The multifactorial threshold model
ternal hypoxia was the cause. To his credit, he put his provided a reasonable answer for this and other prop-
hypothesis to the test and showed that making preg- erties shown by the familial characteristics of pyloric
nant mice hypoxic led to CP in the offspring, another stenosis. Carter and the McGill group went on to show
example of the right conclusion from the wrong infer- that CL had the same characteristic properties of the
ence. model, though to a lesser extent, since the sex ratio for
This, plus the recognition by the Australian oph- CLP was less distorted.
thalmologist Norman McAlister Gregg that rubella was This model implied that CL usually resulted from the
teratogenic and Josef Warkany's demonstration that interaction of several genetic and environmental factors
maternal vitamin deficiencies could be teratogenic in that increased susceptibility and that the particular se-
the rat, led to a shift in attitude toward the causes of lection of factors could be different in different indi-
malformations. The uterus had been regarded as an in- viduals. Thus, identifying the specific factors in the
vulnerable barrier, protecting the embryo from envi- common type of cleft would be much more difficult
v
VI FOREWORD
than it would be for those caused by genes or terato- factors such as prenatal events, susceptibility genes, so-
gens causing major increases in susceptibility. However, cial class, and race. Still, with better appreciation of the
that did not discourage people from trying, as shown problem and more sophisticated statistical approaches,
in Part III of this volume. things are beginning to sort out, as shown in Parts III
Human embryological studies were difficult because and IV.
embryos could be observed only after the fact. The ex- I cannot comment on the clinical side (Section II),
istence of mouse strains with a high frequency of CL except to say how dramatically treatment results have
and of teratogens that could produce high frequencies improved for the whole child, not just the cleft, at least
of CL or CP made it easier to study the embryology of in part because the need for a multidisciplinary ap-
oral clefts and to identify predisposing factors. proach was recognized.
From such studies came Daphne Trasler's idea that Better understanding of causes often takes a long
face shape was one component of CL susceptibility, at time to translate into prevention, but there is progress
least in the mouse. This inspired crude attempts to doc- (Section III). Families with oral clefts can find encour-
ument, with "physioprints" or cephalograms, the rele- agement in knowing that even though their child's cleft
vant components of face-shape susceptibility in the par- was not prevented, there have been great improvements
ents and monozygotic twins of children with CL. These in the management of clefts and their sequelae, coun-
have now been happily supplanted by elegant mor- seling and support of the family, and social attitudes
phometric studies (this volume, Part II). Racial differ- toward malformations. The very recognition of oral
ences in oral cleft frequencies were recognized early, clefts as a public health issue augurs well for affected
but there have been few attempts to relate these to fa- children and their families.
cial morphometrics.
Epidemiological studies are hampered by the fact that F. Clarke Fraser
for an uncommon multifactorial trait it is virtually im- Department of Human Genetics
possible to assemble groups large enough to allow sta- McGill University
tistically valid comparisons of potentially significant Montreal, Canada
Preface
Each year an estimated 150,000 babies are born with cules to tissues and organs (Chapters 1-3). These top-
birth defects in the United States. According to a 1998 ics will be of special interest to basic scientists. Part II,
report of the National Center for Health Statistics, one Chapters 4-8, is devoted to diagnostic and morpho-
in five infant deaths is due to birth defects, making them logical issues. There is still considerable debate on how
the leading cause of infant mortality. Cleft lip with or to classify syndromes associated with clefts. Thus, this
without cleft palate and isolated cleft palate, collec- part will be appealing to both clinicians and re-
tively termed oral clefts, are the second most common searchers. Part III includes methods in oral cleft epi-
birth defects among newborns. It is estimated that ap- demiology (Chapters 9 and 10), the development and
proximately 1 out of every 1000 newborns has an oral use of birth-defect surveillance systems (Chapter 11),
cleft, a figure that is higher in certain ethnic groups. measures of occurrence from international epidemio-
From these statistics it may be concluded that 4000 ba- logical studies (Chapter 12), theories on environmen-
bies are born each year with an oral cleft in the United tal exposures that may increase or decrease the risk of
States. At a lifetime cost of $100,000 per case (ac- oral clef ting (Chapters 13 and 14), and experimental
cording to the National Institute of Dental and Cra- (animal) models for the study of oral clefts (Chapter
niofacial Research in 1998), the expense resulting from 15). Part IV, Chapters 16-23, covers the genetic epi-
this disorder is close to half a billion dollars per annual demiology of oral clefts. This part, of special interest
cohort of such children. to basic researchers and health-policy analysts, de-
Among several objectives of the series Healthy Peo- scribes methodological issues and recent findings.
ple 2010, released by the U.S. Department of Health Cloning and identifying genes associated with disorders
and Human Services in January 2000, are efforts to re- is one of the principal aims of the worldwide Human
duce rates of birth defects and to increase the quality Genome Project. The consequences of these findings,
and years of healthy life in the population. An under- however, are of importance to policy analysts and the
standing of the genetic and environmental factors that public at large.
increase susceptibility to oral clefts is vital to their di- Section II reviews a broad set of clinical approaches
agnosis, treatment, and, eventually, prevention. This to patients and families with oral clefts. Beginning with
book, therefore, is intended to provide graduate stu- a detailed description of the craniofacial team approach
dents, practitioners, and researchers with information (Chapter 24), it deals with pediatric and feeding issues
to help them fulfill the goals of Healthy People 2010. (Chapter 25); surgery (Chapter 26); speech, language,
The book, however, was organized with a wider read- and articulation disorders (Chapter 27); dental care and
ership in mind. Many of the chapters will be of inter- orthodontic treatment (Chapters 28 and 29); associated
est to parents, siblings, and individuals with oral clefts. disorders in the ear, nose, and throat areas (Chapter
The following chapters cover a broad range of the- 30); genetic counseling (Chapter 31); and the psycho-
oretical, experimental, and clinical topics and are writ- logical care of children with oral clefts (Chapter 32).
ten by experts in the fields of craniofacial development, Due to their direct implications for treatment, this sec-
biomedical sciences, genetics, epidemiology, and pub- tion also covers international surgical missions (Chap-
lic health. The format is that of a state-of-the-art ref- ter 33) and evidence-based care for the individual with
erence text for a wide readership seeking in-depth in- an oral cleft (Chapter 34).
formation on oral clefts. The text is divided into three Section III addresses emerging issues that have a di-
sections, Basic Principles, Treatment, and Public Health rect impact on society. Chapter 35 deals with the pre-
Issues, plus one appendix and a glossary. vention of oral clefts through multivitamin supple-
The first section has four parts. Part I presents over- ments. Chapter 36 describes the financial burden
arching principles of facial development, from mole- associated with the care of oral cleft patients, both to
vii
Vlll PREFACE
the family of the affected individual as well as to soci- the public. Education of practitioners and the public is
ety. Coverage of care is discussed in Chapter 37. discussed in Chapter 41, and an example of interna-
Parental perceptions and perspectives on having a child tional collaboration for research and treatment is pre-
with a cleft and on possibilities for treatment and so- sented in Chapter 42. A list of Internet resources is pro-
cial interactions are the subject of Chapter 38, which vided in the Appendix. Finally, a comprehensive
includes compelling stories of parents of children with glossary is included at the end of the volume.
oral clefts. Numerous ethical issues involved in the care Although research findings and strategies for the
of children with craniofacial conditions are discussed treatment of individuals with oral clefts will continue
in Chapter 39. "Translational" methods are presented to evolve in the next decades, I hope that this book will
in Chapter 40. This relatively new discipline aims at be of use to all those who seek specific information in
extending research findings into public health policy any of the areas that are covered here.
and action. This area is at an early stage, but as
presymptomatic genetic tests become increasingly avail- D. F. W.
able, it is receiving much attention from the media and Boston, Massachusetts
Acknowledgments
As the editor of this book, I wish to acknowledge with Sonja Rasmussen, Paul A. Romitti, Amado Ruiz-
gratitude the contributors' investment of time and Razura, Alan F. Scott, Melvin D. Schloss, Gary Shaw,
knowledge in the face of numerous competing demands J. C. Shirley, Robert J. Shprintzen, Keith J. Slifer, Marcy
for their attention. Drafts of each chapter were pre- C. Speer, Kathy K. Sulik, Tsunenobu Tamura, Norman
sented for formal review and comments to at least two J. Waitzman, and Allen Wilcox.
anonymous experts in the respective field. I am grate- My involvement in the field of craniofacial anom-
ful to the following individuals for engaging the con- alies and this book are fruits of the warm support I
tributors in challenging and incisive discussions and for have received from many people since I was a medical
supplying them with detailed comments about their student in Argentina until the present. Some people de-
work: Marlene Anderka, Judith A. Badner, Joan E. serve grateful recognition for inspiring me to fulfill this
Bailey-Wilson, Clint Baldwin, Michael L. Begleiter, dream and for serving as role models: Terri Beaty, Mike
Charles D. Bluestone, Karina Boehm, Dorret Boomsma, Cohen, Jeff Murray, Joan Bailey-Wilson, and Laura
Lorenzo Botto, Rachel Bramson, Alphonse R. Burdi, Mitchell. As the Talmudic sage Rabbi Elazar said: "Al-
Elisa Calzolari, John Canady, Mark A. Canfield, though I learnt a tremendous amount of wisdom from
Francesco Carinci, Suzan Carmichael, Maurizio my teachers, their knowledge was so vast that my learn-
Clementi, Alice Cusner, Muriel Davisson, Douglas S. ing from them could be likened to a dog that laps wa-
Diekema, Virginia M. Diewert, Edward F. Donovan, ter from the ocean."
David L. Duffy, Amy Feldman Lewanda, Ghali Ghali, At Oxford University Press, I am thankful to vice
John M. Graham, Jr., Susan Halloran Blanton, Chris- president Jeffrey House, who lent his support to this
tine Harrison, Jacqueline T. Hecht, Donald V. project from the very beginning, and to production ed-
Huebener, Russell S. Kirby, Deborah Klein Walker, itor Leslie Anglin, who masterfully expedited its pro-
David P. Kuehn, A. Kuijpers-Jagtman, Christopher A. duction. Finally, I acknowledge my lovely wife, Car-
Kus, Edward Lammer, Don LaRossa, Susan Lieff, Ross olien, for her understanding and enduring belief in me,
Long, Jr., Sue Malcolm, Eden R. Martin, Michael Mel- and my three children, Shoshana, Sara, and Daniel,
nick, James Mills, Jeffrey C. Murray, Bonnie L. Padwa, who are my inspiration and the loves of my life.
IX