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Genotype and Cardiac Outcomes in Pediatric Dilated Cardiomyopathy
Journal article   Open access   Peer reviewed

Genotype and Cardiac Outcomes in Pediatric Dilated Cardiomyopathy

Rabia S Khan, Elfriede Pahl, Lisa Dellefave-Castillo, Karen Rychlik, Alexander Ing, Kai Lee Yap, Casey Brew, Jamie R Johnston, Elizabeth M McNally and Gregory Webster
Journal of the American Heart Association, Vol.11(1), e022854
01/04/2022
DOI: 10.1161/JAHA.121.022854
PMCID: PMC9075202
PMID: 34935411
url
https://doi.org/10.1161/JAHA.121.022854View
Published (Version of record) Open Access

Abstract

Background Pediatric dilated cardiomyopathy (DCM) is a well-known clinical entity; however, phenotype-genotype correlations are inadequately described. Our objective was to provide genotype associations with life-threatening cardiac outcomes in pediatric DCM probands. Methods and Results We performed a retrospective review of children with DCM at a large pediatric referral center (2007-2016), excluding syndromic, chemotherapy-induced, and congenital heart disease causes. Genetic variants were adjudicated by an expert panel and an independent clinical laboratory. In a cohort of 109 pediatric DCM cases with a mean age at diagnosis of 4.2 years (SD 5.9), life-threatening cardiac outcomes occurred in 47% (42% heart transplant, 5% death). One or more pathogenic/likely pathogenic variants were present in 40/109 (37%), and 36/44 (82%) of pathogenic/likely pathogenic variants occurred in sarcomeric genes. The frequency of pathogenic/likely pathogenic variants was not different in patients with familial cardiomyopathy (15/33 with family history versus 25/76 with no family history, =0.21). truncating variants occurred in a higher percentage of children diagnosed as teenagers (26% teenagers versus 6% younger children, =0.01), but life-threatening cardiac outcomes occurred in both infants and teenagers with these variants. DCM with left ventricular noncompaction features occurred in 6/6 patients with variants between amino acids 1 and 600. Conclusions Sarcomeric variants were common in pediatric DCM. We demonstrated genotype-specific associations with age of diagnosis and cardiac outcomes. In particular, had domain-specific association with DCM with left ventricular noncompaction features. Family history did not predict pathogenic/likely pathogenic variants, reinforcing that genetic testing should be considered in all children with idiopathic DCM.
 Mutation Adolescent Cardiomyopathy, Dilated Child Genetic Association Studies Genetic Testing Genotype Humans Sarcomeres

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