Genetic diagnosis in the fetus

• Published in: Journal of perinatology Vol. 40; no. 7; pp. 997 - 1006
• Main Authors: Wojcik, Monica H., Reimers, Rebecca, Poorvu, Tabitha, Agrawal, Pankaj B.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2020; Nature Publishing Group
• Subjects: 45/23; 45/61; 692/700/139; 692/700/1720; Amniocentesis; Anencephaly; Aneuploidy; Deoxyribonucleic acid; Diagnosis; Diagnostic systems; DNA; DNA testing; Embryonic development; Embryos; Fetuses; Genetic disorders; Genetic diversity; Genetic screening; Genetic variance; Genetics; Maternal health services; Medical diagnosis; Medicine; Medicine & Public Health; Pediatric Surgery; Pediatrics; Phenotyping; Pregnancy; Pregnant women; Review Article; Sampling; Ultrasound
• ISSN: 0743-8346; 1476-5543
• DOI: 10.1038/s41372-020-0627-z

Many genetic disorders are detectable in the prenatal period, and the capacity to identify them has increased remarkably as molecular genetic testing techniques continue to improve and become incorporated into clinical practice. The indications for prenatal genetic testing vary widely, including follow-up of an anomaly found by routine ultrasound or maternal aneuploidy screening, a family history of genetic disease, advanced maternal or paternal age, or evaluation of a low-risk pregnancy due to parental concern. The interpretation of genetic variants identified in the prenatal period poses unique challenges due to the lack of ability for deep phenotyping as well as the option to make critical decisions regarding pregnancy continuation and perinatal management. In this review, we address the various modalities currently available and commonly used for genetic testing, including preimplantation genetic testing of embryos, cell-free DNA testing, and diagnostic procedures such as chorionic villous sampling, amniocentesis, or percutaneous umbilical blood sampling, from which samples may be sent for a wide variety of genetic tests. We discuss the difference between these modalities for the genetic diagnosis of a fetus, their strengths and weaknesses, and strategies for their optimal use in order to direct perinatal care.