Genetic Testing in Pediatric Cardiomyopathy

Pediatr Cardiol. 2018 Mar;39(3):491-500. doi: 10.1007/s00246-017-1779-2. Epub 2017 Nov 29.


Genetic testing is recommended in patients with dilated cardiomyopathy (DCM); however, limited studies demonstrate high yields of genetic testing in non-hypertrophic (HCM) patients. Furthermore, there is sparse genotype-phenotype data in pediatric DCM patients. We performed a retrospective review of 70 consecutive probands with cardiomyopathy (non-HCM) who underwent genetic evaluation. Mean age at presentation was 5.48 years. Echocardiography revealed mean ejection fraction of 32.4%. The LVEDd z score ranged from - 5.7 to + 15.9. Cardiomyopathy was classified as dilated in 56, 10 with non-compaction, 2 with restrictive, and 2 with ARVC. TTN gene mutations were the most common gene involved. Genetic testing was negative in 16/70 (23%) giving a yield of 77% including VUS. 33% (23/70) of probands had a positive family history among whom the diagnostic yield was 57% (13/23) for pathogenic mutations. Yield for positive genetic testing in the DCM with positive family history group was 9/18 (50%). There were 6 deaths (9%) and 26/70 (37%) underwent transplantation. More frequent cardiac transplantations (48 vs. 34%) and deaths (17 vs. 2%) were seen in mutation-positive vs. mutation-negative subgroups. This study demonstrates an increasing yield of genetic testing in DCM although with a high rate of VUS detection. Use of genetic information for better management and prognostication will require big data analysis.

Keywords: Cardiomyopathy; Dilated; Genetic; Outcome; Pediatric; Restrictive.

MeSH terms

  • Adolescent
  • Cardiomyopathies / genetics*
  • Child
  • Child, Preschool
  • Echocardiography / methods
  • Female
  • Genetic Association Studies
  • Genetic Testing / methods*
  • Genetic Testing / statistics & numerical data
  • Humans
  • Infant
  • Male
  • Mutation
  • Retrospective Studies