Scientific article

Genetic basis of childhood cardiomyopathy

Published inCirculation. Genomic and precision medicine, vol. 15, no. 6, e003686
Publication date2022-12
First online date2022-10-11

Background: The causes of cardiomyopathy in children are less well described than in adults. We evaluated the clinical diagnoses and genetic causes of childhood cardiomyopathy and outcomes of cascade genetic testing in family members.

Methods: We recruited children from a pediatric cardiology service or genetic heart diseases clinic. We performed Sanger, gene panel, exome or genome sequencing and classified variants for pathogenicity using American College of Molecular Genetics and Genomics guidelines.

Results: Cardiomyopathy was diagnosed in 221 unrelated children aged ≤18 years. Children mostly had hypertrophic cardiomyopathy (n=98, 44%) or dilated cardiomyopathy (n=89, 40%). The highest genetic testing diagnostic yields were in restrictive cardiomyopathy (n=16, 80%) and hypertrophic cardiomyopathy (n=65, 66%), and lowest in dilated cardiomyopathy (n=26, 29%) and left ventricular noncompaction (n=3, 25%). Pathogenic variants were primarily found in genes encoding sarcomere proteins, withTNNT2andTNNI3variants associated with more severe clinical outcomes. Ten children (4.5%) had multiple pathogenic variants. Genetic test results prompted review of clinical diagnosis in 14 families with syndromic, mitochondrial or metabolic gene variants. Cascade genetic testing in 127 families confirmed 24 de novo variants, recessive inheritance in 8 families, and supported reclassification of 12 variants.

Conclusions: Genetic testing of children with cardiomyopathy supports a precise clinical diagnosis, which may inform prognosis.

  • Cardiomyopathy
  • Child
  • Family
  • Genetics
  • Sarcomere
  • Adult
  • Humans
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathies / genetics
  • Genetic Testing
  • Cardiomyopathy, Hypertrophic / genetics
  • Heart Diseases / genetics
Affiliation Not a UNIGE publication
Citation (ISO format)
BAGNALL, Richard D et al. Genetic basis of childhood cardiomyopathy. In: Circulation. Genomic and precision medicine, 2022, vol. 15, n° 6, p. e003686. doi: 10.1161/CIRCGEN.121.003686
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Article (Published version)
ISSN of the journal2574-8300

Technical informations

Creation08/28/2023 10:28:49 AM
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