RESUMO
OBJECTIVE: Delineate prenatal features of Costello syndrome (caused by HRAS mutations), which consists of mental retardation, facial, cardiovascular, skin, and musculoskeletal anomalies, and tumor predisposition. METHODS: Literature and new cases classified as Group I (pre-HRAS), Group II (HRAS confirmed), and Group III (HRAS confirmed in natural history study, plus three contributed cases). RESULTS: Polyhydramnios occurred in most (mean 79%) pregnancies of cases in Groups I (98), II (107), and III (17); advanced paternal age and prematurity were noted in approximately half. Less frequent were nuchal thickening, ascites, shortened long bones, abnormal hand posture, ventriculomegaly, macrosomia, and macrocephaly. Fetal arrhythmia occurred in nine cases (six supraventricular or unspecified tachycardia, one unspecified arrhythmia, and two premature atrial contractions, PACs); excluding three new cases and two with PACs, the estimated prenatal frequency is 4/222 (2%). CONCLUSION: Costello syndrome can be suspected prenatally when polyhydramnios is accompanied by nuchal thickening, hydrops, shortened long bones, abnormal hand posture, ventriculomegaly, large size, and macrocephaly, and especially fetal atrial tachycardia. Consideration should be given for timely prenatal diagnostic studies for confirmative HRAS gene mutations and for maternal treatment of serious fetal arrhythmia.
