Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis

his study evaluated the diagnostic yield of exome sequencing in 127 consecutive cases of unexplained nonimmune hydrops fetalis (NIHF), a severe and often lethal fetal condition. The primary outcome was the identification of pathogenic or likely pathogenic genetic variants. Results showed a diagnostic yield of 29%, with RASopathies (disorders affecting the RAS–MAPK pathway) accounting for 30% of the diagnoses. Other identified disorders included inborn errors of metabolism, musculoskeletal conditions, and lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders. The majority of diagnostic variants were autosomal dominant (68%), with 88% being de novo. The study highlights the clinical utility of exome sequencing in NIHF for informing prognosis, recurrence risk, and perinatal management.

his study evaluated the diagnostic yield of exome sequencing in 127 consecutive cases of unexplained nonimmune hydrops fetalis (NIHF), a severe and often lethal fetal condition. The primary outcome was the identification of pathogenic or likely pathogenic genetic variants. Results showed a diagnostic yield of 29%, with RASopathies (disorders affecting the RAS–MAPK pathway) accounting for 30% of the diagnoses. Other identified disorders included inborn errors of metabolism, musculoskeletal conditions, and lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders. The majority of diagnostic variants were autosomal dominant (68%), with 88% being de novo. The study highlights the clinical utility of exome sequencing in NIHF for informing prognosis, recurrence risk, and perinatal management.