Genotype, Phenotypic Severity, and Survival in Pediatric Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry

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.

Authors

Institutions

Publication Details

Journal
Circulation Heart Failure
Published
2026-10-27
DOI
https://doi.org/10.1161/circheartfailure.126.014513
Primary Topic
Cardiomyopathy and Myosin Studies
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Genotype, Phenotypic Severity, and Survival in Pediatric Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry

Steven D. Colan, Daphne T. Hsu, Charles E. Canter, Wendy K. Chung et al.
5 links
Circulation Heart Failure
Cardiomyopathy and Myosin Studies
article

Genotype, Phenotypic Severity, and Survival in Pediatric Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry

Steven D. Colan, Daphne T. Hsu, Charles E. Canter, Wendy K. Chung, Stephanie M. Ware, Brian Feingold, Jean A. Ballweg, Joseph William Rossano, Taye H. Hamza, Lisa Joy Martin, Paul Fraser Kantor, Ling Shi, Irene D. Lytrivi, Steven A. Webber, Melanie D. Everitt, Bruce J. Aronow, Ashwin K. Lal, Elfriede Pahl, Neha M. Bansal, Phillip J. Dexheimer, Surbhi Bhatnagar, Steven E. Lipshultz, Thomas D. Ryan, Jeffrey Allen Towbin, Teresa M. Lee, Jeffery A. Schubert
article en

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.

Circulation Heart Failure
Northwestern University (US), University of Southern California (US), Cincinnati Children's Hospital Medical Center (US), Boston Children's Hospital (US), Primary Children's Hospital (US), Montefiore Medical Center (US), Children's Hospital of Philadelphia (US), Children's Hospital of Los Angeles (US), Harvard University (US), University of Tennessee Health Science Center (US), University of Pittsburgh (US), Washington University in St. Louis (US), University of Utah (US), Columbia University Irving Medical Center (US), NYU Langone Health (US), Children's Hospital Colorado (US), New England Research Institutes (US), Helen DeVos Children's Hospital (US), Children's Hospital at Montefiore (US), Jacobs Institute (US), Le Bonheur Children's Hospital (US), New England Research (United States) (US), Indiana University Indianapolis (US), Indiana University School of Medicine (US), Carelon Research (United States) (US), University of Cincinnati (US), University at Buffalo, State University of New York (US), University of Arkansas for Medical Sciences (US), University of Colorado Denver (US)
Good health and well-being
Openalex Percentile: Top 11%
Cardiomyopathy and Myosin Studies
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.

Laika access coming soon