Comprehensive Versus Targeted Genetic Testing in Children with Hypertrophic Cardiomyopathy
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Updated: Mar 24, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Nathan D Bales1, Nicole M Johnson2,3, Daniel P Judge3
1Johns Hopkins Children's Center M2319, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, 21205, USA.
Insights
Genetic testing for hypertrophic cardiomyopathy (HCM) in children may benefit from broad panels. Children with HCM are more likely to have multiple sarcomere gene mutations than adults.
Area of Science:
- Genetics
- Cardiology
- Pediatrics
Background:
- Hypertrophic cardiomyopathy (HCM) is a genetic sarcomere disease affecting children and adults.
- Current guidelines recommend targeted genetic testing for familial mutations in pediatric HCM cases not representing the first affected family member.
- Clinical observations suggest the possibility of de novo mutations or inheritance from unaffected parents.
Purpose of the Study:
- To analyze genetic findings in patients with HCM undergoing genetic testing.
- To evaluate the frequency of multiple pathogenic mutations in pediatric versus adult HCM patients.
- To inform recommendations for genetic testing strategies in childhood HCM.
Main Methods:
- Retrospective chart review of 239 patients who underwent HCM genetic testing at Johns Hopkins (2004-2013).
- Analysis of personal and familial genetic findings, focusing on sarcomere gene mutations.
- Comparison of mutation prevalence between pediatric and adult HCM cohorts.
Main Results:
- Eighty-one patients had sarcomere gene mutations; 66 were diagnosed with HCM.
- Eight patients (including six children) had more than one pathogenic or likely pathogenic mutation.
- The likelihood of a child with HCM having >1 mutation was 25%, compared to 4.8% in adults.
Conclusions:
- Children diagnosed with HCM, even if not the index case, exhibit a higher prevalence of multiple sarcomere gene mutations.
- Broad genetic panel testing should be considered for children presenting with HCM.
- This approach may improve diagnostic yield and family genetic counseling in pediatric HCM.
Abstract:
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.
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