The impact of genotype-phenotype on the prognosis of children with hypertrophic cardiomyopathy

Objective: To investigate the relationship between different genotypes and clinical phenotypes within a pediatric hypertrophic cardiomyopathy (HCM) population and explore the impact of various genotypes on patient outcomes. Methods: This study involved 82 pediatric HCM patients. A comprehensive review was conducted of echocardiography results, second-generation whole-exome sequencing (WES) findings, and conditions warranting pathologic examination or surgical intervention. Results: WES was performed in 82 children, of whom 65 (79.3%) and pathogenic or likely pathogenic (P/LP) variants. The median patient age was 6.4 years (interquartile range, 3.8- 11.4 years), 45 (54.9%) were male, and 15 (18.3%) had a definitive family history of HCM. The RASopathy group was diagnosed at a significantly younger age compared to the sarcomeric variant HCM group (P = .0017). Female patients were more common (P = .0001) and the rates of right ventricular outflow tract obstruction (P = .026) and biventricular outflow tract obstruction (P = .026) were higher in the RASopathy group. The freedom from early postoperative reobstruction was 83.3% (95% confidence interval [CI], 64.7%-100%) in the no P/LP variant HCM group and 87% (95% CI, 74.2%-100%) in the RASopathy group. The 7-year freedom from reobstruction was 76.3% (95% CI, 59.8%-97.2%). A statistically significant difference in the incidence of left ventricular outflow tract reobstruction was observed between the sarcomeric HCM group and the RASopathy group (P = .025). Linear regression analysis demonstrated a significant association between age and interventricular septal thickness in the RASopathy group (P = .008; r = 0.48). Conclusions: Identifying pathogenic genes in children with HCM enables the assessment of genotype–cardiac phenotype relationships and can guide treatment strategy selection and prognosis, particularly for children with RASopathies.