Abstract 18858: Spectrum of Gene Mutations in Pediatric Hypertrophic Cardiomyopathy
Introduction: Pediatric hypertrophic cardiomyopathies (HCM), a family of genetically heterogeneous diseases characterized by increased left ventricular wall thickness unexplained by ventricular loading, shows a range of severity in clinical outcomes. Many cases remain categorized as idiopathic.
Hypothesis: Sarcomeric protein-gene mutations are commonly associated with HCM in children.
Methods: A convenience sample of unrelated pediatric probands with idiopathic HCM and complete family histories were recruited from 3 institutions. Disease-causing mutations were identified in 6 genes in current genetic testing panels. Proportional differences were examined using a two-sample z test.
Results: The median age at diagnosis was 11 years, 75% were male, and 32% were aged <1 year. We identified mutations in 36 of 38 cases with 3 mutations in 13%, 2 mutations in 21%, and 1 mutation in 58%. Most pathogenic variants were found in cardiac myosin-binding protein (MYBPC3) and β-myosin heavy chain (MYH7) genes (P<0.05). Compared to Richards et al., we found a significantly higher number of pathogenic variants in MYBPC3 in children (12/17; 71%) compared to adults (4/40; 10%, P≤0.001) with similar findings for MHY7 (7/10 vs. 10/40, P=0.007). There was also a significantly higher proportion of children with ≥2 mutations (16/38; 50.0%) compared to adults (4/109; 3.7%; P≤0.001.). The odds ratio for death was 20 (95% CI 1.68, 238.7) in probands with a positive family history of HCM, other cardiomyopathy, or sudden cardiac death compared to negative family history cases.
Conclusions: We found a high incidence of mutations in children with HCM. A family history of cardiomyopathy, sudden cardiac death, pathogenic mutations and abnormal echocardiography should prompt a genetic evaluation. Genetic and echocardiographic testing of relatives could lead to better risk stratification and has potential to stimulate development of therapies based on specific gene mutations.
Author Disclosures: P.R. Barach: None. G.F. Cox: None. J.D. Wilkinson: None. R.L. Thomas: None. S.D. Colan: None. J.A. Towbin: None. A.A. Farooqi: None. C. Cordero: None. S.E. Lipshultz: None.
- © 2016 by American Heart Association, Inc.