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Discordant sex between fetal screening and postnatal phenotype requires evaluation

Journal of Perinatology volume 39, pages 28–33 (2019)Cite this article

Subjects

Abstract

Objective

Non-invasive prenatal screening (NIPS) utilizes circulating cell-free DNA (cfDNA) to screen for fetal genetic abnormalities. NIPS is the first widely-available prenatal screen to assess genotypic sex. Most pediatricians have limited familiarity with NIPS technology and potential etiologies of discordant results. Increased familiarity may provide diagnostic insight and improve clinical care.

Study design

We reviewed all patients with discordant genotypic fetal sex assessed by cfDNA and neonatal phenotypic sex referred to our medical center.

Result

Four infants with discordant cfDNA result and phenotypic sex were identified. Etiologies include vanishing twin syndrome, difference of sexual development, sex chromosome aneuploidy and maternal chimerism.

Conclusions

We present four cases illustrating potential etiologies of discordant cfDNA result and postnatal phenotypic sex. Unanticipated cfDNA results offer the perinatologist a unique opportunity for early diagnosis and targeted treatment of various conditions, many of which may not have otherwise been detected in the perinatal period.

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Acknowledgements

Thank you to Lauren H. Brown, MS; Sheila Weiss, MS; Patricia Fechner, MD; Linda Ramsdell, MS; Margaret Shnorhavorian, MD; Elizabeth McCauley, PhD; Anne-Marie Amies-Oelschlager, MD, and Jane Hitti, MD for their contributions to the patient’s clinical care, enthusiasm for this case series and interesting discussions. Funding support provided by the National Institutes of Health NIH5T32GM007454 (H.M.B.).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Medical Genetics, Stanford University, Palo Alto, CA, USA

    Heather M. Byers

  2. Department of Pathology, Cytogenetics and Genomics Laboratory, University of Washington, Seattle, WA, USA

    Whitney Neufeld-Kaiser

  3. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Washington, Seattle, WA, USA

    Edith Y. Chang & Erin S. Oehler

  4. Department of Laboratories, Seattle Children’s Hospital, Seattle, WA, USA

    Karen Tsuchiya

  5. Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA

    Karen Tsuchiya & Margaret P. Adam

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  1. Heather M. Byers
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Correspondence to Heather M. Byers.

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The authors declare that they have no conflict of interest.

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Byers, H.M., Neufeld-Kaiser, W., Chang, E.Y. et al. Discordant sex between fetal screening and postnatal phenotype requires evaluation. J Perinatol 39, 28–33 (2019). https://doi.org/10.1038/s41372-018-0278-5

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