Diagnostics

Learn how our advanced genetic tests are revolutionizing health

Arrhythmogenic Cardiomyopathy Panel

The Arrhythmogenic Cardiomyopathy Panel is a comprehensive next-generation sequencing (NGS) panel that includes genes related to cardiomyopathy conditions with prominent arrhythmias. This test can be used to confirm a clinical diagnosis or identify at-risk individuals. Disorders of the heart can include abnormalities of the heart muscle (cardiomyopathies), irregularities of the heart’s electrical system leading to irregular heartbeats (arrhythmias), or both. One condition that features cardiomyopathy with prominent arrhythmia is arrhythmogenic right ventricular cardiomyopathy (dysplasia). Arrhythmogenic right ventricular cardiomyopathy is characterized by the progressive replacement of normal heart muscle with fibrous fatty tissue. This predisposes individuals to irregular heart rhythms, including ventricular tachycardia, and sudden death in some cases.

Prevalence

The prevalence of arrhythmogenic right ventricular cardiomyopathy is estimated to be 1 in 1,000 to 1 in 1,250 individuals (Peters, 2006).

Included Disorders

This panel includes genes associated with:

  • Arrhythmogenic right ventricular cardiomyopathy (dysplasia)
  • Hypertrophic cardiomyopathy and arrhythmias
  • Dilated cardiomyopathy and arrhythmias
  • Other conditions that include both cardiomyopathy and arrhythmias as features

Inheritance and Penetrance

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is typically inherited in autosomal dominant manner, although Emery-Dreifuss muscular dystrophy, caused by mutations in the EMD gene, is inherited in an X-linked manner, and Naxos disease, caused by mutations in the JUP gene, is inherited in an autosomal recessive manner. Compound heterozygosity and digenic inheritance has also been reported (Bauce et al, 2010; Xu et al, 2010).


Arrhythmogenic right ventricular cardiomyopathy exhibits reduced penetrance. In one family with a mutation in the DSP gene, the penetrance was 50% (Rampazzo et al, 2002), and in other families with dominant ARVC, the penetrance was estimated at 20-30% (Chowdhury et al, 2005).

Clinical Sensitivity

Disease causing mutations can be identified in approximately 50% of arrhythmogenic right ventricular cardiomyopathy cases (Quarta et al, 2011). The Arrhythmogenic Right Ventricular Cardiomyopathy Panel includes all of the genes commonly associated with this disease.

Methodology and Analytical Sensitivity

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent intron/exon boundaries, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity of the assay is 99.5%.

Indications for Testing

  • Confirmation of a clinical diagnosis
  • Unexplained cardiac arrest
  • Cardiomyopathy and arrhythmia
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of arrhythmogenic right ventricular cardiomyopathy or other arrhythmogenic cardiomyopathy

Included Genes (20)

ACTN2 EMD PLN TGFB3
DES JUP PRKAG2 TMEM43
DSC2 LDB3 RBM20 TNNI3
DSG2 LMNA RYR2 TNNT2
DSP PKP2 SCN5A TTN

Additions to Arrhythmogenic Cardiomyopathy Panel

Emerging Evidence Genes (3)

Emerging evidence genes can also be added on to the Arrhythmogenic Cardiomyopathy panel. These genes do not have a clear association with arrhythmogenic cardiomyopathy, but emerging evidence suggests that they may play a role in disease.

ANKRD1
CTNNA3
PDLIM3

References

  1. Bauce B, Nava A, Beffagna G, et al. Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm. 2010;7(1):22-9.
  2. Peters S. Advances in the diagnostic management of arrhythmogenic right ventricular dysplasia-cardiomyopathy. Int J Cardiol. 2006;113(1):4-11.
  3. Quarta G, Muir A, Pantazis A, et al. Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria. Circulation. 2011;123(23):2701-9.
  4. Rampazzo A, Nava A, Malacrida S, et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002;71(5):1200-6.
  5. Sen-chowdhry S, Syrris P, Mckenna WJ. Genetics of right ventricular cardiomyopathy. J Cardiovasc Electrophysiol. 2005;16(8):927-35.
  6. Xu T, Yang Z, Vatta M, et al. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol. 2010;55(6):587-97.