Clinical role of genetic testing for overlapping between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy

Abstract

Abstract Background/Introduction Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are inherited arrhythmias that may predispose to sudden cardiac arrest. Although its pathogenetic mechanisms differ, overlapping features between BrS and ARVC have been demonstrated previously. However, it remains to be determined whether genetic testing for ARVC-related gene is needed in patients with BrS. Purpose This study is aimed to analyze genetic profiles of BrS patients using next generation sequencing (NGS) based multigene panel including ARVC related genes. Methods Patients who were confirmed as BrS or clinically suspected as BrS with type 2 or 3 Brugada pattern electrocardiography were studied. Genetic testing using NGS panels (Illumina Inc., San Diego, CA, USA) included 30 genetic variants associated with inherited arrhythmia and genetic cardiomyopathy. Results Among the total 119 patients from BrS registry, 63 patients were confirmed as BrS and 56 patients were clinically suspected as BrS without fulfilling diagnostic criteria. One-hundred-fourteen patients (95.8%) were male, and mean age of onset was 43.6 year-old. Genetic variants were identified in 25 of 42 patients who received genetic testing. Six out of 25 patients (24.0%) showed ARVC-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) (Figure 1 and Table 1). None of the patients showed structural or electrocardiographic features that fulfill diagnostic criteria of ARVC. It is notable that ARVC-related genotypes were mostly frequently accounted for BrS patients, following SCN5A and SCN10A. Conclusion In the clinic setting, ARVC-related genetic variants were identified in significant proportion of BrS patients, supporting that genetic testing of ARVC-overlapping is needed. This study suggests that follow-up including imaging study should be considered in BrS patients with ARVC-related genotypes to monitor disease progression as ARVC. Funding Acknowledgement Type of funding sources: None.