Genetic variants were not linked to initial DCM severity in children

In a prospective, multicenter cohort of 279 children with nonsyndromic dilated cardiomyopathy, researchers identified pathogenic or likely pathogenic variants in 19%. Variant status was not associated with heart failure symptoms, echocardiographic severity, or death or transplant during follow-up.

Pathogenic or likely pathogenic variants were identified in 19%.
Variant status was not associated with initial disease severity.
Death or transplant exceeded 60% by 10 years.
Normalization trend by variant status was not statistically significant.

Researchers studied 279 children aged 0–18 years with nonsyndromic dilated cardiomyopathy (DCM), enrolled prospectively across multiple institutions from 2013 to 2016. Exome sequencing examined 37 cardiomyopathy-associated genes. The median age at diagnosis was 1.6 years, and median follow-up was 1.1 years. Outcomes included death, cardiac transplant, persistent left ventricular dysfunction, and echocardiographic normalization.

Pathogenic or likely pathogenic variants were found in 18 genes and in 19% of the cohort. The most frequently implicated genes were TTN (17% of positive variants), TNNT2 (15%), MYH7 (15%), RBM20 (9%), and LMNA (8%). Genetic yield was highest among children older than 12 years, at 34%. Heart failure symptoms and echocardiographic severity were not associated with variant status. Death or transplant rates also did not differ by status; the combined outcome exceeded 60% by 10 years after diagnosis. Echocardiographic normalization showed a nonsignificant trend toward being more frequent in children without an identified variant (P=0.09).

The findings suggest that a negative panel does not indicate milder disease at diagnosis. The cohort’s median follow-up was relatively short, and the 10-year outcome estimates extend beyond that median; the abstract does not provide further detail on long-term follow-up or variant interpretation limitations.

In practice

For children with nonsyndromic DCM, this cohort found that identifying a pathogenic or likely pathogenic variant did not distinguish initial heart failure symptoms or echocardiographic severity, and was not associated with death or transplant rates. Genetic testing identified a cause in 19%, with higher yield in children older than 12 years. These observational findings do not establish that genotype lacks prognostic value in every setting; median follow-up was 1.1 years, and the reported 10-year combined event rate exceeded 60%.

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Source

Circulation: Heart Failure: Genotype, Phenotypic Severity, and Survival in Pediatric Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry ↗

This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.