Genetic Disorders and the Fetus, Sixth Edition

1191 Pages·2009·32.441 MB·English

Genetic Disorders
and the Fetus
Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment
Sixth Edition Edited by Aubrey Milunsky and Jeff M. Milunsky
© 2010 Aubrey Milunsky and Jeff Milunsky. ISBN: 978-1-405-19087-9
Dedicated to
Laura and Kiran
For their love, support and understanding
and to
our grandchildren and children,
Julie, Miranda, and Cody,
who endow life with joy and meaning
“ Make assurance double sure. ”
Shakespeare, MacBeth
Genetic Disorders
and the Fetus
Diagnosis, Prevention
and Treatment
EDITED BY
Aubrey Milunsky
MB BCh, DSc, FRCP,
FACMG, DCH
Professor of Human Genetics, Pediatrics, Pathology, and
Obstetrics and Gynecology,
Co-Director, Center for Human Genetics
Boston University School of Medicine and Boston Medical Center
Boston, MA, USA
Jeff M. Milunsky
MD, FACMG
Professor of Pediatrics and Genetics and Genomics
Co-Director, Center for Human Genetics
Director, Clinical Genetics
Boston University School of Medicine and Boston Medical Center
Boston, MA, USA
SIXTH EDITION
A John Wiley & Sons, Ltd., Publication
This edition fi rst published 2010, © 2010 by Aubrey Milunsky and Jeff Milunsky
Previous editions: 1979, 1986, 1992, 1998, 2004 © Aubrey Milunsky
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ISBN: 978-1-4051-9087-9
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1 2010
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x
1 Genetic Counseling: Preconception, Prenatal and Perinatal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Aubrey Milunsky and Jeff M. Milunsky
2 Amniocentesis and Fetal Blood Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Sherman Elias
3 Amniotic Fluid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Aubrey Milunsky
4 Amniotic Fluid Cell Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
Daniel L. van Dyke
5 Prenatal Genetic Diagnosis through Chorionic Villus Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
Giovanni Monni, Rosa Maria Ibba and Maria Angelica Zoppi
6 Prenatal Diagnosis of Chromosomal Abnormalities through Amniocentesis . . . . . . . . . . . . . . . . . . . . . 194
Peter A. Benn
7 Prenatal Diagnosis of Sex Chromosome Abnormalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Jeff M. Milunsky
8 Molecular Cytogenetics and Prenatal Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Stuart Schwartz
9 Prenatal Diagnosis and the Spectrum of Involvement from Fragile X Mutations . . . . . . . . . . . . . . . . . . 349
Randi Hagerman, Vivien Narcisa and Paul Hagerman
10 Prenatal Diagnosis by Microarray Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Joris Robert Vermeesch
11 Molecular Genetics and Prenatal Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380
John A. Phillips III
12 Prenatal Diagnosis of Disorders of Lipid Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Bryan G. Winchester
13 Prenatal Diagnosis of the Peroxisomal and Mitochondrial Fatty Acid Oxidation Defi ciencies . . . . . . . 489
Ronald J.A. Wanders
14 Prenatal Diagnosis of the Mucopolysaccharidoses and Postnatal Enzyme Replacement Therapy . . . . . 495
John J. Hopwood
15 Disorders of the Metabolism of Amino Acids and Related Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 514
Vivian E. Shih and Roseann Mandell
16 Prenatal Diagnosis of Disorders of Carbohydrate Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 554
Yuan-Tsong Chen and Deeksha S. Bali
17 Prenatal Diagnosis of Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577
Gerald L. Feldman and Kristin G. Monaghan
v
vi Contents
18 Prenatal Diagnosis and Treatment of Congenital Adrenal Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . 600
Phyllis W. Speiser
19 Prenatal Diagnosis of Miscellaneous Biochemical Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 614
David S. Rosenblatt and David Watkins
20 Prenatal Diagnosis of Primary Immunodefi ciency Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 628
Jennifer M. Puck
21 Prenatal Diagnosis of the Hemoglobinopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646
John M. Old
22 Prenatal Diagnosis of Disorders of Bone and Connective Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 680
Andrea Superti-Furga and Sheila Unger
23 Maternal Serum Screening for Neural Tube and Other Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 705
Aubrey Milunsky and Jacob A. Canick
24 Multi-Marker Maternal Serum Screening for Chromosomal Abnormalities . . . . . . . . . . . . . . . . . . . . . . 771
Howard S. Cuckle and Peter A. Benn
25 Prenatal Diagnosis of Fetal Malformations by Ultrasound . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 819
Yves G. Ville and Durata Nowakowska
26 Prenatal Diagnosis and Management of Abnormal Fetal Development with Emphasis on the
Third Trimester of Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 882
Juriy W. Wladimiroff and Titia E. Cohen-Overbeek
27 Prenatal Diagnosis by Fetal Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 911
Nadine Girard and Kathia Chaumoitre
28 Induced Abortion for Genetic Indications: Techniques and Complications . . . . . . . . . . . . . . . . . . . . . . . 929
Lee P. Shulman
29 Preimplantation Genetic Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 950
Yury Verlinsky* and Anver Kuliev
30 Prenatal Diagnosis through Analysis of Intact Fetal Cells and Cell-Free Nucleic Acids in the
Maternal Circulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 978
Diana W. Bianchi and Y.M. Dennis Lo
31 Fetal Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1001
Diana L. Farmer, Hammin Lee, Elizabeth Gress, Aubrey Milunsky and Michael R. Harrison
32 Prenatal Diagnosis of Fetal Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1020
Yves Ville and Guillaume Benoist
33 Medicolegal Aspects of Prenatal Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1053
Ellen Wright Clayton and Mary Z. Pelias
34 Prenatal and Preimplantation Diagnosis: International Policy Perspectives . . . . . . . . . . . . . . . . . . . . . . 1081
Bartha Maria Knoppers and Thu Minh Nguyen
35 Ethical Issues in the Diagnosis and Management of Genetic Disorders in the Fetus . . . . . . . . . . . . . . 1097
Frank A. Chervenak and Laurence B. McCullough
Appendix, Prenatal Diagnosis of Additional Miscellaneous Genetic Disorders . . . . . . . . . . . . . . . . . . . . . . . 1122
Aubrey Milunsky
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1136
Color plate appears facing page 948
* Deceased.
Preface
In the search for accurate and reliable information, about application of this new technology, which
a discerning reader would welcome a source that is constantly being refi ned, to preimplantation
reliably dispenses evidence - based facts embellished genetic diagnosis (PGD). The second addition is
by knowledge, experience and wisdom. This the chapter that is focused on the social, legal and
precious distillate, tinctured with recommenda- public policy issues with special reference to inter-
tions and guidance born of long experience, is not national approaches to prenatal diagnosis. The
reachable by the most avid electronic voyeur. third addition expands previous coverage of the
Sifting through mountains of unfi ltered, irrelevant, important peroxisomal and related fatty acid oxi-
unreliable or misleading information, electronic dation disorders.
searches simply spawn reams of paper, mostly The fundamental pillars of this sixth (and
lacking critical analysis of the subject in question. earlier) edition(s) are represented by the other 32
At best, authors will describe “ limitations ” in their chapters which are replete with the factual basis of
studies, while awaiting guidance from their clinical prenatal diagnosis, synthesis, critical analysis and
Colleges or Societies, which often takes years. guidelines. In the opening chapter, the principles
Fortunately this volume, a major repository of and practice that underscore preconception, pre-
facts about prenatal diagnosis, provides a critical natal and perinatal genetic counseling is presented
analysis and synthesis of established and new in detail with emphasis on lessons learned since the
knowledge based on the long experience of author- inception of prenatal genetic diagnosis. An enor-
ities in their respective fi elds. The guidance pro- mous factual base is provided in a chapter on
vided and the insights and perspectives of these amniotic fl uid function and constituents including
authors make this volume a valuable and indispen- pesticides, carcinogens and other environmental
sable resource for all whose focus is securing fetal contaminants, while the essentials of cell culture
health through prenatal diagnosis. for prenatal diagnosis are provided in another.
A broad international perspective is presented Chapters on amniocentesis and fetal blood sam-
in this volume with authoritative contributions pling, and chorion villus sampling are anchored by
from authors in nine countries. All chapters have authors with a lifetime of experience. Prenatal
been revised and updated, new guidelines empha- chromosome diagnosis, the bedrock upon which
sized, and three new important chapters added. this subject was built, is again captured in an
The fi rst addition is the use of chromosomal authoritative extensive chapter that is pertinent to
microarrays in prenatal diagnosis. Clinical trials, all engaged in prenatal diagnosis, and enhanced by
now underway, will help determine the frequency a separate chapter on molecular cytogenetics and
of detecting a microdeletion/duplication of clinical the use of fl uorescent in situ hybridization.
signifi cance which would have otherwise been Clear guidance is provided for the genetic coun-
missed by routine cytogenetics. At the same time, seling and management following the frequently
a clear measure should emerge of how often copy incidental prenatal diagnosis of a sex chromosome
number variations of uncertain signifi cance are disorder, while the Fragile X syndrome is exten-
determined and how often they are deemed “ prob- sively addressed by pioneers. Recent and continu-
ably benign ” . Compounding the normal anxiety ing advances in molecular genetics now command
expectant mothers experience during prenatal a central role in prenatal diagnosis refl ected by the
diagnosis with signifi cant degrees of uncertainty many serious monogenic disorders amenable to
will not only be unhelpful, but may cause harm if early detection. Comprehensive, authoritative
unnecessary pregnancy termination is pursued. and important chapters on biochemical genetics
Major reservation is expressed in this chapter encompass much that is known about the prenatal
vii
viii Preface
diagnosis of the lipid storage disorders, the muco- sequencing of fetal DNA, are described and assessed
polysaccharidoses, the organic and amino acid and in a re - written expert chapter.
related disorders of metabolism, the disorders of Advances in fetal therapy, either directly or
carbohydrate metabolism, the peroxisomal and via the maternal circulation, have continued and
related fatty acid oxidation disorders and the dis- require attention given opportunities to intervene,
orders of folate and cobalamin metabolism. especially where surgical or medical treatment can
Revised and updated chapters on cystic fi brosis, save the fetus, as described in two re - written and
congenital adrenal hyperplasia and the primary revised chapters. Cogent issues of law, ethics and
immunodefi ciency disorders are followed by a public policy as they apply to prenatal diagnosis are
masterly discourse on the hemoglobinopathies. explored in depth by acknowledged experts in the
New advances combining molecular genetics and three last chapters. Greater public awareness of
fetal imaging provide valuable information in the genetics has alerted many to the opportunities of
re - written chapter on connective tissue disorders. preventing adverse outcomes in pregnancy. One
An extremely thorough exposition of maternal consequence has been escalating litigation by those
serum screening for neural tube defects, Down deprived of the chance to avoid harm, which is also
syndrome and chromosome abnormalities, occu- discussed in the fi rst chapter.
pies two chapters refl ecting current practice. Bio- This reference text, with contributions uniquely
chemical screening for neural tube defects heralded fi rst authored by senior professors and directors,
previously as one of the most important advances is a veritable repository of information on prenatal
in prenatal diagnosis, may well be largely replaced genetic diagnosis, is very heavily referenced, full of
soon by ultrasonography once the technical skills guidance and refl ective of the lifetime experience
have been universally mastered. and wisdom of the authors. This addition encom-
Sophisticated ultrasonic imaging for fetal struc- passes 162 tables, 129 fi gures, including 14 color
tural and functional abnormalities are superbly plates, and nearly 9000 references. An extensive table
covered in two updated chapters, while the growing of additional disorders amenable to prenatal diag-
importance of fetal magnetic resonance imaging in nosis is added as an appendix. A valuable index will
resolving diffi cult diagnostic quandaries is expertly enrich the reader ’ s search for specifi c information.
covered in a re - written chapter. Exciting progress marks the 45 th year since the
Any attempt at prenatal diagnosis must be pre- introduction of prenatal cytogenetic diagnosis
ceded by counseling at which time the provider by amniocentesis and cell culture. Major recent
must be fully informed about the details if induced advances include signifi cant progress in the devel-
abortion will need to be considered. An updated opment of chromosomal microarrays, gene dis-
expert revision of a chapter on the subject provides covery and fast next - generation gene sequencing,
the necessary facts and guidance to be shared with a fetal imaging, non - invasive prenatal diagnosis and
patient. Avoidance of abortion is facilitated by pre- preimplantation genetic diagnosis. We hope that
implantation genetic diagnosis (PGD) which is fully this edition will once again provide evidence - based
updated in a revised chapter detailing a remarkable guidance, insight and perspective, combined with
array of achieved diagnoses. Screening for aneu- an enormous factual base. Recognition of many
ploidy prior to implantation seems common sense, new and unresolved challenges should provide
but uniform supportive data are lacking, some con- inspiration for novel research initiatives. Mostly
cluding that randomized controlled trials are however we hope that the progress mirrored in this
needed, while others maintain that suffi cient data volume and the anticipated progress will help reas-
exists to indicate an unfavor able practice. Clearly, sure many parents at risk that they can avoid either
more defi nitive research is required. conceiving offspring with serious/lethal genetic
Among the most anticipated and exciting disorders or having affected offspring that could
developments is non - invasive prenatal diagnosis have been detected prenatally.
by analysis of fetal DNA and RNA in the mater-
nal circulation. The technological innovations, Aubrey Milunsky and Jeff M. Milunsky
now developing rapidly and including shot - gun Boston
Acknowledgments
Only rarely does one encounter a major reference which fetal and maternal health and welfare are
text in which every chapter is written by an paramount will be the benefi ciaries of the informa-
acknowledged authority or internationally recog- tion and guidance proffered. We are extremely
nized expert. Such is the nature of this sixth edition grateful to all our authors for their superb
in which outstanding physicians, scientists and contributions.
academicians have again considered it worthy to We are also most grateful to my senior executive
have taken the time to share their expertise, experi- secretary, Mrs. Marilyn McPhail, who yet again
ence, and wisdom. Readers in many disciplines in effectively demonstrated the art of multi - tasking.
ix
List of Contributors
Deeksha S. Bali, PhD, FACMG Ellen Wright Clayton, MD, JD
Assistant Professor and Laboratory Director Pediatrics, Rosalind E. Franklin Professor of Genetics and Health
Division of Medical Genetics, Duke University Medical Policy, Director, Center for Biomedical Ethics and Society;
Center, Durham, NC, USA Professor of Pediatrics; Professor of Law; Vanderbilt
University, Nashville, TN, USA
Peter A. Benn, MSc, PhD, FACMG, DSc
Professor, Departments of Genetics and Developmental Titia E. Cohen- Overbeek, MD, PhD
Biology, Pediatrics, and Laboratory Medicine; and Senior Physician Prenatal Medicine, Erasmus University
Director, Human Genetics Laboratories, University of Medical Center, Department of Obstetrics and
Connecticut Health Center, Farmington, CT, USA Gynecology, Rotterdam, the Netherlands
Guillaume Benoist, MD Howard S. Cuckle, MSc, DPhil
Department of Obstetrics and Gynecology, Centre Adjunct Professor, Obstetrics and Gynecology, Colombia
Hospitalier Intercommunal de Poissy - St. Germain en University, New York, NY, USA and Emeritus Professor,
Laye, Poissy, France Reproductive Epidemiology, University of Leeds, Leeds, UK
Diana W. Bianchi, MD Sherman Elias, MD, FACOG, FACMG,
Natalie V. Zucker Professor of Pediatrics, Obstetrics and FACS
Gynecology and Vice - Chair for Research and Academic John J. Sciarra Professor and Chair, Department of
Affairs, Department of Pediatrics, Tufts University Obstetrics and Gynecology, Feinberg School of Medicine,
School of Medicine; Tufts Medical Center, Boston, MA, Northwestern University, and Prentice Women ’ s Hospital,
USA Chicago, IL, USA
Jacob A. Canick, PhD, FACB Diana L. Farmer, MD
Professor, Department of Pathology and Laboratory Professor of Surgery, Pediatrics, and Obstetrics,
Medicine, The Warren Alpert Medical School of Brown Gynecology and Reproductive Sciences; Chief, Division
University; and Director, Division of Prenatal and Special of Pediatric Surgery, and Vice Chair, Department of
Testing, Women and Infants Hospital, Providence, RI, Surgery, University of California, San Francisco and
USA Surgeon - in - Chief, UCSF Children ’ s Hospital, San
Francisco, CA, USA
Yuan - Tsong Chen, MD, PhD
Professor of Pediatrics and Genetics, Duke University Gerald L. Feldman, MD, PhD
Medical Center, Durham, NC, USA and Institute of Professor, Center for Molecular Medicine and Genetics,
Biomedical Sciences, Academia Sinica, Taiwan and Departments of Pediatrics and Pathology, Wayne State
University School of Medicine; Director, Clinical Genetics
Frank A. Chervenak, MD Services, and Director, Molecular Genetics Diagnostic
Given Foundation Professor and Chair, Department of Laboratory, Detroit Medical Center - University
Obstetrics and Gynecology and Gynecologist - in - Chief, Laboratories, Detroit, MI, USA
New York - Presbyterian Hospital and Weill Medical
College of Cornell University, New York, NY, USA Nadine Girard, MD, PhD
Professor of Neuroradiology, Centre de Resonance
Kathia Chaumoitre, MD, PhD Magnetique Biologique et Medicale,, Centre National
Laboratorire d ’ anthropologie, Faculte de Medicine de la Recherche Scientifi que, Faculte de Medicine la
Marseille, Universite de la Mediterranee, France and Timone, Marseille, France, Universite de la Mediterranee,
Department of Radiology, Hopital Nord, Marseille, and Head of Neuroradiology, Timone Hospital, Marseille,
France France
x