Mutation and Phenotypic Spectrum of Patients With RASopathies

To examine the common and specific clinical features, mutation spectrum and genotype-phenotype correlation in Noonan syndrome and related RASopathies.

Records of 30 patients with clinical diagnosis of Noonan syndrome and related RASopathies presenting over a six-year period at a tertiary care medical genetics centre were reviewed. Detailed clinical phenotype evaluation and genetic testing (PTPN11 sequencing or next generation sequencing) was done. The genetic results were used to classify the patients.

Noonan syndrome was confirmed in 22 patients, 5 had cardiofaciocutaneous syndrome and 3 had Noonan syndrome like disorder with loose anagen hair. The molecular diagnosis was confirmed in 27 patients. Mutations in PTPN11 gene were confirmed in 57.8 % patients. Developmental delay, cardiac defects, ectodermal abnormalities and coarse face was the predominant phenotype. Noonan syndrome like disorder with loose anagen hair was clinically identifiable by the sparse, slow growing hair and caused by one recurrent SHOC2, c.4A>G mutation.

Noonan syndrome and other RASopathies should be suspected in patients with short stature, cardiac defects, typical facial dysmorphism with or without ectodermal involvement.