Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study From the Pediatric Cardiomyopathy...

Area of Science:

• Genetics
• Cardiology
• Pediatrics

Background:

• Myocarditis patients may carry more cardiomyopathy-associated genetic variants than the general population.
• Data on genetic variants in children with myocarditis is limited.
• This study investigates genetic variants in children with dilated cardiomyopathy (DCM) secondary to myocarditis.

Purpose of the Study:

• To compare the prevalence of rare predicted-damaging and clinically pathogenic variants in children with DCM secondary to myocarditis versus children with DCM alone and healthy controls.
• To assess the genetic burden associated with myocarditis in pediatric DCM cases.

Main Methods:

• Exome sequencing data from the Pediatric Cardiomyopathy Registry was analyzed for children with DCM (with and without myocarditis).
• Heart-healthy controls were matched 4:1 on genomic similarity.
• Bioinformatics and clinical guidelines were used to identify and classify rare predicted-damaging and pathogenic variants in cardiomyopathy-associated genes.

Main Results:

• Children with DCM secondary to myocarditis had a significantly higher prevalence of rare predicted-damaging variants (34.4%) compared to controls (6.3%).
• Pathogenic/likely pathogenic variants were found in 12.5% of myocarditis cases but 0% of controls.
• No significant difference in variant prevalence was observed between children with DCM secondary to myocarditis and those with DCM alone.

Conclusions:

• Children with DCM secondary to myocarditis exhibit an increased burden of variants in cardiomyopathy-associated genes compared to healthy controls.
• Further research with larger cohorts is necessary to determine the clinical utility of routine genetic testing in pediatric myocarditis patients.