Genotype, Phenotypic Severity, and Survival in Pediatric Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry
In brief
Only 1 in 5 children with dilated cardiomyopathy had an identified genetic cause
In a 279-child study, testing found a disease-associated gene variant in 19%, with higher detection among children diagnosed after age 12. A genetic finding did not track with heart failure symptoms, heart ultrasound severity, or death or transplant; those outcomes were similarly poor, while heart function tended to normalize more often without an identified variant.
- Journal
- Circulation. Heart failure (Q1)
- Published
- 27 October 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Paul F Kantor, Stephanie M Ware, Wendy K Chung, Lisa J Martin, Taye Hamza, Ling Shi, et al.
- PMID
- 42935448
- DOI
- 10.1161/CIRCHEARTFAILURE.126.014513
Why clinicians should know about it
- Picked for Genetics (clinical) (top studies of the week, 1 November 2026): Pediatric cardiomyopathy genetic yield and genotype–outcome associations
Abstract
BACKGROUND: 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, TTN (17%), TNNT2 (15%), MYH7 (15%), RBM20 (9%), and LMNA (8%) were most frequently implicated. Only 19% of the overall cohort yielded an identifiable genetic cause, without any difference between ancestries. Children >12 years old had the highest genetic yield at 34% (P<0.05). Symptoms of heart failure occurred in 62% of patients who carried a pathogenic/LP gene variant, at or within 12 months of presentation, but neither heart failure symptoms, nor echocardiographic severity was associated with having a pathogenic/LP variant. The rate of death or cardiac transplant did not differ with the presence or absence of a pathogenic/LP variant and exceeded 60% by 10 years after diagnosis. On competing risks analysis, a trend (P=0.09) toward greater echo normalization, was noted in those without a pathogenic/LP variant by 10 years after diagnosis. 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.