Key result
Pathogenic gene variants fail to predict 10-year death or transplant in pediatric DCM.
Why the study?
Dilated cardiomyopathy frequently presents with heart failure in children, but whether a genetic cause is associated with disease severity or eventual outcome in pediatric DCM was unclear.
Does the presence of a pathogenic or likely pathogenic genetic variant influence clinical severity, survival, cardiac transplant rates, or echocardiographic normalization in children with nonsyndromic dilated cardiomyopathy?
Cohort (n=279)
Yes
Does the presence of a pathogenic or likely pathogenic genetic variant influence clinical severity, survival, cardiac transplant rates, or echocardiographic normalization in children with nonsyndromic dilated cardiomyopathy?
In pediatric dilated cardiomyopathy, pathogenic or likely pathogenic gene variants are detected in only 19% of patients and do not predict disease severity at diagnosis or rates of death and cardiac transplantation, although patients without identified variants show a trend toward higher rates of echocardiographic normalization.
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.
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Kantor et al. (2026) conducted a cohort in Pediatric nonsyndromic dilated cardiomyopathy (DCM) (n=279). Pathogenic or likely pathogenic (LP) cardiomyopathy gene variant vs. Absence of a pathogenic/LP gene variant was evaluated on Clinical severity and outcomes of death, cardiac transplant, and continuing left ventricular dysfunction versus echocardiographic normalization (p=0.09). Pathogenic/LP gene variants were found in 19% of pediatric DCM patients and did not alter 10-year death/transplant rates (>60%), though non-carriers trended toward greater echo normalization (P=0.09).
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