Phenotypic and genotypic spectrum of noonan syndrome: A retrospective analysis of 46 consecutive pediatric patients presented at a regional cardiac center in China.

Background: Noonan syndrome (NS) is relatively common but poorly recognized. We aimed to describe the phenotypic and genotypic spectrum of NS in a Chinese cohort.

Method: The study retrospectively investigated consecutive pediatric patients who presented at the Guangdong cardiovascular institute between 2018 and 2020 with confirmed known NS-relevant mutations determined by exome sequencing. Dates of genetic testing, Age, sex, institution of genetic testing, mutated gene (related to NS) and its classification, heterozygosity, and parental origin were identified from the sequencing reports. Facial features, cardiac defect and other clinical characteristics were also assessed. Comparisons of categorical variables between groups were examined by Chi-square test or Fisher's exact test when appropriate. Intraclass correlation coefficient (ICC) was performed to evaluate the reliability of evaluation of facial features between different evaluators.

Results: The most prevalent mutated genes were PTPN11 (37.0%) and RAF1 (19.6%), and most mutations were pathogenic (67.4%) and de novo (87.0%). Most patients were with NS-relevant facial features (97.4%) and cardiac defects (92.7%), where ventricular hypertrophy, pulmonary valve stenosis, and atrial septal defect were the most prevalent. Patients with mutated RAF1 appeared to be diagnosed at an older age than those with mutated PTPN11, and with higher prevalence of mitral regurgitation, hypertrophic cardiomyopathy, and ventricular hypertrophy, but lower prevalence of pulmonary valve stenosis and pulmonary artery stenosis. Patients presented at an age ≥2 years appeared to be with fewer NS-relevant facial features and cardiac defects than those aged <2 years.

Conclusions: These findings indicated featured distributions of phenotypic and genotypic spectrum in Chinese pediatric patients, which might be helpful for early NS diagnosis.