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, Gregory Webster*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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, P=0.21). TTN truncating variants occurred in a higher percentage of children diagnosed as teenagers (26% teenagers versus 6% younger children, P=0.01), but life-threatening cardiac outcomes occurred in both infants and teenagers with these TTN variants. DCM with left ventricular noncompaction features occurred in 6/6 patients with MYH7 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, MYH7 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.

Original languageEnglish (US)
Article numbere022854
JournalJournal of the American Heart Association
Issue number1
StatePublished - Jan 4 2022


  • Dilated cardiomyopathy
  • Genotype
  • Pediatrics
  • Transplant

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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