Prenatal features of Noonan syndrome: prevalence and prognostic value

Abstract

Objective: Noonan syndrome (NS) is a common autosomal dominant developmental disorder, mainly characterized by congenital heart defects, short stature, and a variable degree of developmental delay. We have reviewed the prenatal findings in NS and we have correlated them with genotype and postnatal phenotype.

Methods: The cohort consisted of 47 patients with molecular diagnosis of NS. Prenatal and postnatal phenotypes were assessed by analysis of medical records, and clinical follow-up. Postnatal clinical phenotype, congenital heart disease, neuropsychomotor development, and growth pattern were arbitrarily scored in terms of severity.

Results: Mean age at diagnosis of NS was 7 years (ranging from birth to 38 years). Abnormal maternal serum triple screen was present in 36% of cases, nuchal translucency > 2.5 mm in 41%, polyhydramnios in 38% and fetal anomalies at prenatal ultrasonography in 21%. No statistical association was observed between prenatal findings and NS genotype or scores of postnatal clinical phenotype, congenital heart disease, neuropsychomotor development, or short stature. Presence of morphologic fetal anomalies at ultrasonography was associated with developmental delay/intellectual disabilities (p < 0.001) and juvenile myelomonocytic leukaemia (p = 0.006).

Conclusions: Abnormal prenatal findings are frequent in NS pregnancies, though they are not specific and most are not useful for the prediction of the postnatal phenotype.