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Pathogenic variants associated with dilated cardiomyopathy predict outcome in pediatric myocarditis

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Item Type:Article
Title:Pathogenic variants associated with dilated cardiomyopathy predict outcome in pediatric myocarditis
Creators Name:Seidel, F. and Holtgrewe, M. and Al-Wakeel-Marquard, N. and Opgen-Rhein, B. and Dartsch, J. and Herbst, C. and Beule, D. and Pickardt, T. and Klingel, K. and Messroghli, D. and Berger, F. and Schubert, S. and Kühnisch, J. and Klaassen, S.
Abstract:BACKGROUND: Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome. METHODS: A cohort of 42 patients (MYCPEDIG) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. MYCPEDIG patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (MYC-NonDCM) and 20 patients with DCM (MYC-DCM). RESULTS: MYC-DCM patients (median age 1.4 years) were younger than MYC-NonDCM patients (median age 16.1 years; p<0.001) and were corresponding to heart failure-like and coronary syndrome-like phenotypes, respectively. At least one likely pathogenic/pathogenic (LP/P) variant was identified in 9/42 patients (22%), 8 of them were heterozygous, and 7/9 were in MYC-DCM. LP/P variants were found in genes validated for primary DCM (BAG3, DSP, LMNA, MYH7, TNNI3, TNNT2, and TTN). Rare variant enrichment analysis revealed significant accumulation of high impact disease variants in MYC-DCM versus healthy individuals (p=0.0003). Event-free survival was lower (p=0.008) in MYC-DCM patients compared to MYC-NonDCM and primary DCM. CONCLUSIONS: We report heterozygous LP/P variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of LP/P variants, and poor outcome. These phenotype- and age-group specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.
Keywords:Myocarditis, Cardiomyopathy, Genetics, Next Generation Sequencing, Pediatrics
Source:Circulation Genomic and Precision Medicine
ISSN:2574-8300
Publisher:American Heart Association
Volume:14
Number:4
Page Range:e003250
Date:4 August 2021
Official Publication:https://doi.org/10.1161/CIRCGEN.120.003250
PubMed:View item in PubMed

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