Sex differences in Brugada syndrome

The Brugada syndrome (BrS), one of the most devastating causes of sudden cardiac death in relatively young patients with apparently normal hearts, was originally termed in 1992. According to the recent consensus conference of J wave syndromes in 2016, only spontaneous type 1 Brugada-ECG pattern is the basis for the diagnosis of BrS. Mutations which affect cardiac ion currents have been linked to the syndrome, however strong evidence of link to the disease has been established only for the cardiac sodium channel gene SCN5A. Because all mutations thus far identified in SCN5A display an autosomal dominant mode of transmission, males and females would be expected to inherit the defective gene equally, however, Brugada-ECG pattern phenotype is 8 to 10 times more prevalent in men than in women. Moreover, malignant BrS is surprisingly uncommon in females, representing less than 10% of the patient population with arrhythmic events (AEs). This explains the difficulty of accurately comparing the clinical, ECG, electrophysiologic and genetic characteristics of males and females with BrS and AEs. In the present chapter we will review the main sex differences in BrS patients.