Whole-genome sequencing in prenatally detected congenital malformations: prospective cohort study in clinical setting.

We demonstrate a diagnostic yield of 26% with clinical WGS in prenatally detected congenital malformations. Our study emphasizes the benefits that WGS can bring to the diagnosis of fetal structural anomalies. It is important to note that causative chromosome aberrations were excluded from our cohort before WGS. As chromosome aberrations are a well-known cause of prenatally detected congenital malformations, future studies using WGS as a primary diagnostic test, including assessment of chromosome aberrations, will most likely show that the detection rate will exceed the diagnostic yield of this study. WGS can hereby add clinically relevant information, explaining the underlying cause of the fetal anomaly, which will provide information concerning the specific prognosis of the condition as well as estimate the risk of recurrence. A genetic diagnosis can also provide more reproductive choices in future pregnancies. This article is protected by copyright. All rights reserved.