Mutations in the MYH7 and MYBPC3 genes account for approximately 50%1 of cases of hypertrophic cardiomyopathy (HCM). But HCM can also be caused by pathogenic variants in many genes (genetic heterogeneity), including seven additional sarcomeric genes (MYBPC3, TNNT2, TPM1, MYL2, MYL3, TNNI3, ACTC1).
Further complicating the HCM picture are disorders such as Pompe disease, Fabry disease, PRKAG2‐cardiomyopathy, Danon disease, TTR‐amyloidosis, and other conditions due to mitochondrial dysfunctions that present with HCM and phenotypically mimic isolated HCM.2
Dilated cardiomyopathy (DCM) is also inherited with more than 60 genes that have been associated with disease in various studies.4 Traditional testing using gene panels is generally accepted in patients with familial DCM, in the absence of an environmental cause.2,3 In these patients, the genetic yield can be as high as 55%. Genetic testing is recommended for all patients with familial DCM to facilitate screening. In comparison, guideline recommendations for testing in patients with sporadic DCM vary, but specific clinical features might increase the yield of testing and warrant testing consideration.5
To assist with and streamline genetic testing for inherited cardiomyopathies with overlapping phenotypes, PerkinElmer Genomics offers its exome sequencing, which screens for single nucleotide variations, deletion/duplications, and mtDNA genes associated with HCM and DCM, along with Brugada syndrome, Long QT syndrome, and other cardiomyopathies. This testing can uncover an underlying molecular cause that can lead to accurate clinical diagnosis and management for patients.
- Marian AJ and Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 2017; 121(7):749–770.
- Mazzarotto F, et al. Contemporary insights into the genetics of hypertrophic cardiomyopathy: Toward a new era in clinical testing? J Am Heart Assoc 2020; 9(8):e015473.
- Mestroni L, et al. Genetic causes of dilated cardiomyopathy. Prog Pediatr Cardiol 2014; 37(1-2): 13–18.
- Japp AG, et al. The diagnosis and evaluation of dilated cardiomyopathy. J Am Coll Cardiol 2016; 67:2996–3010.
- Rosenbaum AN, et al. Genetics of dilated cardiomyopathy: practical implications for heart failure management. Nat Rev Cardiol 2020; 17:286–297.