Genotype, Phenotypic Severity, and Survival in Pediatric Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry
Paul F. Kantor, Stephanie M. Ware, Wendy K. Chung, Lisa J. Martin, Taye Hamza, Ling Shi, Steven D. Colan, Joseph W. Rossano, Jeffrey A. Towbin, Teresa M. Lee, Ashwin K. Lal, Steven Webber, Charles E. Canter, Daphne T. Hsu, Melanie D. Everitt, Elfriede Pahl, Neha Bansal, Jean A. Ballweg, Brian Feingold, Irene D. Lytrivi, Thomas D. Ryan, Surbhi Bhatnagar, Bruce J. Aronow, Phillip J. Dexheimer, Jeffery A. Schubert, Steven E. LipshultzBACKGROUND:
Dilated cardiomyopathy (DCM) frequently presents with heart failure in children. Whether a genetic cause of DCM is associated with disease severity or eventual outcome in pediatric DCM is unclear.
METHODS:
A multiinstitutional prospective pediatric cohort study (0–18 years) with nonsyndromic DCM was undertaken from 2013 to 2016. A panel of 37 cardiomyopathy-associated genes was interrogated by exome sequencing with analysis for pathogenic or likely pathogenic (LP) variants. Clinical severity and outcomes of death, cardiac transplant, and continuing left ventricular dysfunction versus echocardiographic normalization were assessed.
RESULTS:
A total of 279 DCM probands (47% male) with a median (interquartile range) age at diagnosis of 1.6 (0.4–10.4) years were enrolled. Median follow-up was 1.1 (0.2–4.0) years. Gene variants designated as pathogenic/LP were identified in 18 of the 37 genes evaluated, and of all positive variants,
CONCLUSIONS:
A genetic cause was detected in a minority of children and was not associated with the phenotypic severity of DCM at diagnosis. Echocardiographic normalization of left ventricular function over time was noted more frequently in patients who did not have an identified pathogenic/LP variant.