Sparks TN, Lianoglou BR, Adami RR, et al. - Researchers here examined the extent to which exome sequencing can aid in the diagnosis of nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal and has numerous genetic causes. A series of 127 consecutive unexplained cases of NIHF was evaluated; the series were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, raised nuchal translucency, or a combination of these conditions. In nearly one-third of the cases, they recognized diagnostic genetic variants, including those for disorders affecting the RAS–MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Among the cases with diagnostic variants, 68% were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. Potentially diagnostic variants were identified in an additional 12 cases.