High Diagnosis Rate for Nonimmune Hydrops Fetalis With Prenatal Clinical Genome: Expanded Results From the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study

Heterogeneous monogenic causes identified by prenatal exome sequencing, then by genome sequencing in undiagnosed cases

The HYDROPS study assessed the yield of prenatal exome sequencing in nonimmune hydrops fetalis after a negative standard workup, then the incremental yield of genome sequencing in cases without a definitive diagnosis. Across 50 exomes, 22 diagnoses were made (44%) and six possible diagnoses (12%). Nine of the 28 newly reported cases (68%) received a diagnosis involving RIT1, SOS1, RYR1, FLT4, LMOD2, KMT2D, PUF60 or BLTP1, and two additional cases were diagnosed after reclassification of uncertain variants. Genome sequencing of eligible exome cases yielded an incremental diagnostic rate of 7% (1 of 14).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A 44% yield from prenatal exome sequencing in nonimmune hydrops after a negative workup is a strong argument for offering sequencing up front rather than as a last resort, in an indication where the decision window is very short. The incremental yield of genome over exome, at 1 in 14, remains marginal at this sample size and does not yet justify a systematic switch. Also worth noting: two additional diagnoses came from simple reanalysis of uncertain variants, confirming that deferred review is part of the pathway rather than an optional extra.

Analysis by Dr Thibaut Benquey