An incidental finding in prenatal exome sequencing-A case study and review of the clinical and ethical considerations

Am J Med Genet A. 2023 Dec;191(12):2856-2859. doi: 10.1002/ajmg.a.63372. Epub 2023 Aug 14.

Abstract

The introduction of genomic testing into prenatal care has come at a rapid pace and has been met with significant clinical and ethical challenges, specifically when dealing with incidental findings. We present the case of a couple in their first pregnancy who were referred to our institution with isolated fetal cataracts on morphology scan. After an unremarkable infectious disease workup and microarray on an amniocentesis sample, the couple opted for fetal whole-exome sequencing to investigate the cataracts further. This investigation did not find any cause for the cataracts but yielded an incidental finding of a de novo pathogenic variant in the SCN1A gene unrelated to the cataracts. Pathogenic variants in the SCN1A gene are strongly associated with severe myoclonic epilepsy of infancy, or Dravet syndrome. After extensive genetic counseling, the couple decided to terminate the pregnancy at 28 weeks' gestation based on this finding. This case highlights some of the important clinical and ethical considerations in prenatal genetic diagnosis, particularly in the group of patients in which there is no phenotypic evidence in-utero of the incidental finding. The case demonstrates the value of frameworks and guidelines to guide management decisions for both clinicians and patients.

Keywords: SCN1a mutation; congenital cataracts; incidental findings; prenatal exome sequencing; secondary findings.

Publication types

  • Case Reports

MeSH terms

  • Cataract*
  • Epilepsies, Myoclonic* / genetics
  • Exome Sequencing
  • Female
  • Humans
  • Incidental Findings
  • Pregnancy
  • Prenatal Diagnosis