Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome

Aims Brugada syndrome (BrS) is a life-threatening arrhythmia disorder associated with autosomal-dominant mutations in the SCN5A gene. We aimed to characterize the diagnostic challenges and clinical manifestations of a novel SCN5A mutation associated with BrS. Methods and results From a novel SCN5A mutation (c.664C>T; p.Arg222X) identified in a proband with the characteristic electrocardiographic pattern and the history of sudden collapse, 122 family members were studied including 40 carriers of the mutation. The electrocardiographic diagnosis of BrS requires type 1 Brugada electrocardiogram (ECG) pattern in >1 right precordial lead (V1–V3), but recently an isolated lead with coved-type ECG was proposed to be enough for the diagnosis. In this family, these proposed criteria (PC) were more sensitive in detecting mutation carriers than the conventional criteria without repercussion on the specificity. Carriers had, on average, longer P-wave duration, PR, and QRS intervals and higher transmural dispersion of repolarization. The prevalence of late potentials was higher in carriers, and individual signal average ECG (SAECG) parameters (QRSf, LAS, and RMS40) also were related to SCN5A gene mutation. Three non-carriers were found to be affected by BrS, two with a spontaneous type 1 ECG with alternative placement of the precordial electrodes, and one only after the pharmacological provocative test, suggesting that other genes may play a role in the pathophysiology of this disease. Conclusion The PC for BrS diagnosis should be implemented. Some parameters from the spontaneous ECG and the SAECG are more effective tools than the characteristic repolarization pattern to discriminate between carriers of SCN5A mutations.