From diagnostic yield to clinical impact: a pilot study on the implementation of prenatal exome sequencing in routine care

Genet Med. 2019 Oct;21(10):2303-2310. doi: 10.1038/s41436-019-0499-9. Epub 2019 Mar 28.

Abstract

Purpose: Exome sequencing (ES) is an efficient tool to diagnose genetic disorders postnatally. Recent studies show that it may have a considerable diagnostic yield in fetuses with structural anomalies on ultrasound. We report on the clinical impact of the implementation of prenatal ES (pES) for ongoing pregnancies in routine care.

Methods: We retrospectively analyzed the impact of pES on pregnancy outcome and pre- or perinatal management in the first 22 patients counseled for pES because of one or more structural anomalies on fetal ultrasound.

Results: In two cases, a diagnosis was made by chromosomal microarray analysis after ES counseling. The remaining 20 cases were divided in three groups: (1) pES to aid parental decision making (n = 12), (2) pES in the context of late pregnancy termination requests (n = 5), and (3) pES to guide pre- or perinatal management (n = 3). pES had a clinical impact in 75% (9/12), 40% (2/5), and 100% (3/3) respectively, showing an overall clinical impact of pES of 70% (14/20).

Conclusion: We show that clinical implementation of pES is feasible and affects parental decision making or pre- and perinatal management supporting further implementation of ES in the prenatal setting.

Keywords: clinical impact; exome sequencing; fetal anomalies; parental counseling; perinatal management.

MeSH terms

  • Exome / genetics
  • Exome Sequencing / ethics*
  • Exome Sequencing / methods*
  • Female
  • Fetus / diagnostic imaging
  • Genetic Counseling / methods
  • Humans
  • Pilot Projects
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Retrospective Studies
  • Ultrasonography, Prenatal / methods