关键词: Noonan综合征, PTPN11基因, RAF1基因, 肥厚型心肌病, 先天性心脏病

Abstract:

Objective To retrospectively summarize the genetic variants and clinical characteristics of Noonan syndrome in children with hypertrophic cardiomyopathy (HCM). Methods A total of 123 children with HCM were enrolled in this study. Second generation sequencing and bioinformatic analysis of 96 genes associated with hypertrophic cardiomyopathy were performed in 123 probands. Eleven patients with diagnosed with Noonan syndrome, and their clinical data and echocardiographic findings were collected. Results The median age of diagnosis of HCM was 2 years and 7 months (5 months to 10 years), and the median age of diagnosis of Noonan syndrome was 6 years and 9 months (7 months to 16 years). 10 of 11 children had variants in RAF1 gene on chromosome 3, one had variant in PTPN11 gene on chromosome 12, and 7 had other novel variants. One of the patients with RAF1 was also found carrying variant in MYBPC3 which is associated with HCM. Nine out of 11 patients with HCM had typical facial features of Noonan syndrome. All 11 children had hypertrophic cardiomyopathy, 9 with obstructive hypertrophic cardiomyopathy, 2 with right ventricular outflow tract obstruction, and 7 with congenital heart disease. Conclusion RFA1 mutation is commonly seen in children with HCM in Noonan syndrome. Those patients carried with RFA1 mutation are more likely to have left ventricular outflow track obstruction and congenital heart diseases.

Key words: Noonan syndrome, PTPN11 gene, RAF1 gene, hypertrophic cardiomyopathy, congenital heart disease