Current perspectives on risk prediction and genetic basis of Brugada syndrome

Brugada syndrome (BrS) is an inherited arrhythmia disorder and a major cause of sudden cardiac death below 50 years. Despite more than three decades of research, diagnosis and risk prediction remain challenging due to variable presentation and incomplete understanding of its genetic basis. The Brugada electrocardiographic pattern is central to diagnosis but lacks specificity, while different scoring systems offer structured assessment yet perform inconsistently in asymptomatic or intermediate-risk patients. SCN5A is the only gene with definitive evidence for causality, but incomplete penetrance and polygenic effects limit its clinical utility. Important gaps remain, including the low diagnostic yield of genetic testing, the unclear course of asymptomatic BrS patients with spontaneous type I electrocardiographic pattern and in geno-negative BrS patients, and the limited validation of current risk models. In this mini review, we explore these challenges and discuss new directions, that could move the field toward more accurate and personalized management.