Genetic basis of hypertrophic cardiomyopathy in children

tefan Rupp, Moataz Felimban, Anne Schänzer, Dietmar Schranz, Christoph Marschall, Martin Zenker, Thushiha Logeswaran, Christoph Neuhäuser, Josef Thul, Christian Jux, Andreas Hahn; Clin Res Cardiol (2018). doi:10.1007/s00392-018-1354-8

42 patients with the diagnoses of HCM made before age 18 years were treated in our center from 2000 to 2016. Genetic analysis was performed in 36 subjects, a genetic defect was detected in 29 (78%) patients. 15 individuals (42%) had pathogenic variants in genes encoding sarcomere proteins, and 5 (14%) in genes coding for components of the RAS/MAPK signaling pathway. 4 subjects (11%) had mutations in the GAA gene (Pompe disease), and 3 (8%) had Frataxin repeat expansions (Friedreich’s ataxia). One patient each showed a mutation in BAG3 and LMNA. Discussion of unsolved HCM cases after performing next-generation sequencing (28 genes) in an interdisciplinary board unraveled the genetic cause in 9 subjects (25%).
A definite genetic diagnosis can be reached in nearly 80% with HCM of childhood onset. Next-generation sequencing in conjunction with a multidisciplinary cooperation can enhance the diagnostic yield substantially. This may be important for risk stratification, treatment planning and genetic counseling.

 Genetic basis of hypertrophic cardiomyopathy in children