Evolving Features of RASopathies Among Pregnancies With Abnormal Fetal Fluid Collections

We aimed to characterize the fetal features across gestation and describe genotype-phenotype correlations for pregnancies with fetal RASopathies that were more severely affected as they presented with at least one abnormal fluid collection.

Retrospective cohort study of pregnancies with a fetal RASopathy and one or more abnormal fluid collections. Ultrasound and clinic databases were searched at six institutions to identify pathogenic or likely pathogenic variants indicating a fetal RASopathy. Phenotypic features were organized by gestational age to evaluate their evolution, and chi-square and Fisher exact proportions were compared.

Forty-six pregnancies were included. Pleural effusions, skin edema, ascites, and cardiac abnormalities presented across gestation. Cystic hygroma and jugular sacs presented in the first trimester and persisted into the second trimester. Hepatomegaly, polyhydramnios, small or absent stomach, and contractures were more frequent in the second and third trimesters. Contractures were more likely with HRAS variants (63% vs. 24%, p = 0.044) and increased nuchal translucency or cystic hygroma were more common with SOS1 variants (100% vs. 44%, p = 0.049).

These data provide insight into genotype-phenotype correlations and the course of fetal RASopathies that present with at least one abnormal fluid collection. Timing of these phenotypes is important to consider for future research on targeted in utero approaches to management.