Related Experiment Video
Updated: Jan 9, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study From the Pediatric Cardiomyopathy
Alicia M Kamsheh1, Stephanie M Ware2, Surbhi Bhatnagar3
1Department of Pediatrics, Division of Pediatric Cardiology, Washington University School of Medicine, St. Louis, MO (A.M.K., C.E.C.).
Insights
Children with myocarditis-induced dilated cardiomyopathy (DCM) show a higher prevalence of genetic variants linked to heart conditions compared to healthy children. This finding highlights potential genetic predispositions in pediatric myocarditis cases.
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.
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.
More Related Videos
07:15Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
09:36Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
Published on: December 22, 2023
Related Concept Videos
01:25Cardiomyopathy I: Introduction and Classification
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:30Cardiomyopathy II: Dilated Cardiomyopathy
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
01:21Myocarditis I: Introduction
01:29Cardiomyopathy V: Interprofessional Care