Key result
RASopathy variants are linked to differing LVOT reobstruction rates versus sarcomeric variants in pediatric HCM.
Why the study?
The relationship between different genotypes and clinical phenotypes in pediatric hypertrophic cardiomyopathy, and the impact of these genotypes on patient outcomes, required investigation.
How do different genotypes impact clinical phenotypes and prognosis in pediatric hypertrophic cardiomyopathy?
Observational (n=82)
How do different genotypes impact clinical phenotypes and prognosis in pediatric hypertrophic cardiomyopathy?
Absolute Event Rate: 87% vs 83.3%
Identifying pathogenic genes in pediatric HCM reveals distinct genotype-phenotype correlations, with RASopathies showing earlier onset and higher rates of outflow tract obstruction, which can guide treatment and prognosis.
May support genotype-stratified postoperative monitoring in pediatric HCM; hypothesis-generating and requires prospective validation.
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.
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A 2025 study conducted an observational in Pediatric hypertrophic cardiomyopathy (n=82). RASopathy variants vs. Sarcomeric variants or no pathogenic variants was evaluated on Freedom from early postoperative reobstruction. In pediatric hypertrophic cardiomyopathy, the incidence of left ventricular outflow tract reobstruction differed significantly between the RASopathy and sarcomeric variant groups (P=0.025).
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