Genetic mutations in 5 causative desmosomal genes account for only 30% to 50% of patients with arrhythmogenic right ventricular cardiomyopathy, with compound or digenic heterozygosity frequently seen.
Highlights the complex genetics of ARVC and emphasizes that cascade genetic testing in family members is only useful when a causative mutation is identified in the proband.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically transmitted disease. However, the genetics are more complex than in other inherited conditions wherein a single gene abnormal mutation may be causative. In ARVC, 5 causative desmosomal genes have been identified, but because only 30% to 50% of patients with ARVC have 1 of these gene abnormalities, it is assumed that there are other genes not yet identified. Frequently, patients with ARVC have >1 genetic defect in the same gene (compound heterozygosity) or in a second complementary gene (digenic heterozygosity). In addition, a family member may have an ARVC gene defect and have development of the disease or have no or minimal manifestations of the disease. Clinical genetic testing is commercially available. It is beneficial for first-degree family members of a person with ARVC to have genetic testing but only if there is a known genetic abnormality in the affected person. If the affected family member (proband) with ARVC does not have a genetic defect identified, then it will not be identified in the family member. Genetic counseling is strongly advised for family members of the proband.
Marcus et al. (Thu,) conducted a review in Arrhythmogenic right ventricular cardiomyopathy (ARVC). Genetic testing was evaluated. Genetic mutations in 5 causative desmosomal genes account for only 30% to 50% of patients with arrhythmogenic right ventricular cardiomyopathy, with compound or digenic heterozygosity frequently seen.