2025-12-05 バッファロー大学(UB)
<関連情報>
- https://www.buffalo.edu/news/releases/2025/12/Genetics-role-children-myocarditis-heart-failure.html
- https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.125.013104
小児心筋炎における心筋症関連病原性変異:小児心筋症レジストリからの研究 Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study From the Pediatric Cardiomyopathy Registry
Alicia M. Kamsheh, MD, MSCE, Stephanie M. Ware, MD, PhD, Surbhi Bhatnagar, PhD, Lisa J. Martin, PhD, Teresa M. Lee, MD, MS, Jeffrey A. Towbin, MD, Paul F. Kantor, MBBCh, … ,and Steven E. Lipshultz, MD
Circulation: Heart Failure Published: 5 December 2025
DOI:https://doi.org/10.1161/CIRCHEARTFAILURE.125.013104
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.
