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Library of Congress Cataloging-in-Publication Data
Names: Milunsky, Aubrey, editor. | Milunsky, Jeff M., editor.
Title: Genetic disorders and the fetus : diagnosis, prevention, and
treatment / edited by Aubrey Milunsky, MB BCh, DSc, FRCP, FACMG, DCH
and Jeff M. Milunsky, MD, FACMG.
Description: Eighth edition. | Hoboken, NJ : Wiley-Blackwell, 2021.
Identifiers: LCCN 2021058739 (print) | LCCN 2021058740 (ebook) | ISBN
9781119676935 (hardback) | ISBN 9781119676973 (adobe pdf) | ISBN
9781119676959 (epub)
Subjects: LCSH: Prenatal diagnosis. | Fetus–Diseases–Genetic aspects. |
Fetus–Abnormalities–Genetic aspects.
Classification: LCC RG628 .G46 2021 (print) | LCC RG628 (ebook) | DDC
618.3/2075–dc23
LC record available at https://lccn.loc.gov/2021058739
LC ebook record available at https://lccn.loc.gov/2021058740
Cover Design: Wiley
Cover Image: © (Left column): Rasi Bhadramani/iStock/Getty Images.
(Top row)(left) Roland Axt-Fliedner and Aline Wolter; (center) Liesbeth van Leeuwen,
Malou A. Lugthart, and Eva Pajkrt; (right) Liesbeth van Leeuwen, Malou A. Lugthart, and
Eva Pajkrt. (Middle row)(left) Nadine Girard and Kathia Chaumoitre; (center) Nadine Girard
and Kathia Chaumoitre; (right) Michael A. Belfort and Alireza A. Shamshirsaz.
(Bottom row)(left) Anver Kuliev and Svetlana Rechitsky.
Preface
Certainty and trust are the hallmarks of prenatal diagnosis where doubt and ambiguity are outlaws. At no time was that more apparent than when AM made his first prenatal genetic diagnosis over 50 years ago. “Are you sure?” were that patient's first words, intoned with deep anxiety. Those words underscored the still cogent need for accuracy in prenatal diagnosis, where mostly a single report would be final. That was a time when prenatal diagnosis depended on amniocentesis‐based study, yielding an accuracy rate exceeding 99 percent. Few laboratory tests, then or now, concerned with profoundly important decision‐making equal this enviable accuracy. Variants of uncertain significance had not yet entered the genetic lexicon.
Today, however, with the newer, beguiling, noninvasive technology, amniocentesis and chorionic villus sampling (CVS) use has declined dramatically. On the altars of convenience and expediency, women are choosing or simply encouraged to have noninvasive prenatal testing, often blissfully unaware that about half of all chromosomal abnormalities detectable through amniocentesis or CVS and authoritatively discussed, would be missed. There is room for concern given the current consensus that all women should be offered either of these two procedures.
Similarly, all women with risks of having offspring with a monogenic disorder and a known pathogenic variant should be informed about and offered the option of preimplantation genetic testing (PGT). The extensive and long‐established experience of the authors with PGT enshrine this recommendation. Expanded carrier screening should make this a more frequently addressed option. Couples should, however, be carefully counseled about the limitations of such screening. All the facts, figures, guidelines, and recommendations have been updated in this edition, and will assist the expanded healthcare team in providing optimal care to all patients.
Coupled with remarkable advances in technology, prenatal diagnosis has undergone a revolution. Thus far, and continually increasing, more than 4,331 culprit genes and 6,739 associated phenotypes for an extensive array of genetic disorders have been identified. Consequently, since physicians in all medical specialties encounter genetic disorders for which a molecular diagnosis is available, awareness of the options for prenatal diagnosis or PGT has become especially important.
Pari passu with these technical advances has come the opportunity to avoid and prevent the occurrence of many lethal and seriously disabling genetic diseases. This progress means that physicians in all specialties incur responsibility (and inevitable liability) to acquire new knowledge of genetic disorders and offer appropriate tests or refer patients for evaluation and genetic counseling.
More than 60 million people worldwide are estimated to have DNA studies in the next 5 years. Expanded carrier testing, maternal cell‐free plasma DNA testing, whole‐exome sequencing, next‐generation sequencing, single‐cell molecular diagnosis, and advanced fetal imaging, all fully presented in this volume, now complement the well‐established procedure for prenatal diagnosis and PGT. Whole‐genome analysis for prenatal diagnosis (even if advisable) simply awaits further technical advances.
Chromosomal
