Circ Heart Fail. 2025 Dec 5:e013104. doi: 10.1161/CIRCHEARTFAILURE.125.013104. Online ahead of print.
ABSTRACT
BACKGROUND: Studies have demonstrated that patients with myocarditis may have a higher burden of cardiomyopathy-associated genetic variants than the general population. However, data on children are limited. We compared the prevalence of rare predicted-damaging variants and clinically pathogenic variants in children with dilated cardiomyopathy (DCM) secondary to myocarditis with that in children with DCM alone and in heart-healthy controls.
METHODS: Children with DCM secondary to myocarditis and children with DCM alone who underwent exome sequencing as part of a prior cross-sectional study were identified in the Pediatric Cardiomyopathy Registry, a large multicenter registry of children with cardiomyopathy. Controls from the Indiana University Biobank were matched 4:1 with myocarditis cases on genomic similarity. Rare predicted-damaging variants in cardiomyopathy-associated genes were identified using a bioinformatics approach. Clinical guidelines were used to determine clinical pathogenicity. The prevalence of variants was compared across the 3 groups.
RESULTS: There were 32 patients with DCM secondary to myocarditis. The prevalence of rare predicted-damaging variants was 34.4% (11/32 [95% CI, 18.6%-53.2%]) in cases compared with 6.3% (8/128 [95% CI, 2.7%-11.9%]) in controls (P<0.001). Clinical review indicated all rare predicted-damaging variants in cases were pathogenic (1/12), likely pathogenic (3/12), or variants of uncertain significance (8/12), whereas most variants in controls were benign (2/8) or likely benign (4/8). The prevalence of pathogenic/likely pathogenic variants in cases was 12.5% (95% CI, 3.5%-29.0%) compared with 0% (95% CI, 0%-2.3%) in controls (P<0.01). Rare predicted-damaging and clinically pathogenic/likely pathogenic variant prevalence was not significantly different in children with DCM secondary to myocarditis and DCM without myocarditis (P=0.17 and P=1.00, respectively).
CONCLUSIONS: Children with DCM secondary to myocarditis had a higher burden of variants in cardiomyopathy-associated genes than that of heart-healthy controls. Larger studies will be needed to determine the utility of routine genetic testing in this population.
PMID:41347311 | DOI:10.1161/CIRCHEARTFAILURE.125.013104
