Comprehensive Versus Targeted Genetic Testing in Children with Hypertrophic Cardiomyopathy

Pediatr Cardiol. 2016 Jun;37(5):845-51. doi: 10.1007/s00246-016-1358-y. Epub 2016 Mar 2.


Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere that can be found in both children and adults and is associated with many causative mutations. In children who are not the index case of HCM in their families, current recommendations call only for targeted genetic testing for familial mutations. However, clinical experience suggests that de novo mutations are possible, as are mutations inherited from apparently an unaffected parent. A chart review was conducted of all patients who received HCM genetic testing at Johns Hopkins from 2004 to 2013. In total, 239 patient charts were analyzed for personal and familial genetic findings. Eighty-one patients with sarcomere gene mutations were identified, of which 66 had a clinical diagnosis of HCM. Importantly, eight patients had >1 pathogenic or likely pathogenic mutation, including six patients who were diagnosed with HCM as children (18 or younger). In this analysis, when a sarcomere mutation is identified in a family, the likelihood of a child with HCM having >1 mutation is 25 % (6/24), compared to 4.8 % (2/42) for adults. The large number of children with multiple mutations suggests that broad panel rather than targeted genetic testing should be considered in HCM presenting during childhood even if the child is not the index case.

Keywords: Genetic counseling; Genetic testing; Hypertrophic cardiomyopathy.

MeSH terms

  • Cardiomyopathy, Hypertrophic*
  • Child
  • Genetic Testing
  • Humans
  • Mutation
  • Sarcomeres