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Genetic diagnosis in the fetus

Journal of Perinatology volume 40, pages 997–1006 (2020)Cite this article

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Abstract

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.

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Fig. 1: Opportunities for prenatal genetic evaluation.
Fig. 2: Overview of embryonic development and its relevance to prenatal genetic testing.

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Acknowledgements

MHW is supported by UM1HG008900. The authors thank the patients and families that we care for at our respective institutions and at the Maternal Fetal Care Center at Boston Children’s Hospital, who continue to teach and inspire us.

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Authors and Affiliations

  1. Division of Newborn Medicine, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Monica H. Wojcik, Tabitha Poorvu & Pankaj B. Agrawal

  2. Division of Genetics and Genomics, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Monica H. Wojcik, Rebecca Reimers & Pankaj B. Agrawal

  3. The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA, USA

    Monica H. Wojcik & Pankaj B. Agrawal

  4. Division of Maternal-Fetal Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Rebecca Reimers

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MHW and PBA conceived of and outlined the manuscript, which MHW drafted and all authors critically reviewed and edited.

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Correspondence to Monica H. Wojcik or Pankaj B. Agrawal.

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Wojcik, M.H., Reimers, R., Poorvu, T. et al. Genetic diagnosis in the fetus. J Perinatol 40, 997–1006 (2020). https://doi.org/10.1038/s41372-020-0627-z

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