Genetic heterogeneity in Noonan syndrome: evidence for an autosomal recessive form

Abstract

Most Noonan syndrome (NS) families are compatible with autosomal dominant inheritance with predominance of maternal transmission. Sporadic patients can be explained by new autosomal dominant mutations. Here we report four Dutch NS patients, two male and two female, each with unaffected consanguineous parents. All four had a typical NS phenotype and presented with hypertrophic obstructive cardiomyopathy (HOCM) at birth. In two cases the HOCM improved, in one case it deteriorated, and in one case it remained constant over 12 years. These patients support the existence of an autosomal recessive form of NS in which HOCM is more frequent than in autosomal dominant NS.