BrS was first described in 1989 as a hereditary condition involving VT/VF, SCD in normal hearts. It was later linked to loss-of-function mutations in SCN5A gene encoding the cardiac Na+ channel, but mutations in this gene are only found in ~20% of patients. Variants in 19 genes affecting Na+, K+, Ca2+, and funny currents have been implicated, but caution is needed in interpretation as not all variants contribute significantly to the BrS phenotype. Scn5a mutations have also been linked to SSS, PCCD, idiopathic VF, and overlap disorders, with the same mutation affecting different family members differently due to other modifying factors.
BrS was thought to be the cause of 12% of SCD cases in the general population (Brugada and Brugada, 1992), but recent studies show its prevalence is lower. Southeast Asians have a higher risk for BrS but only 0.1% showed a Brugada pattern. In China, the overall BrS pattern prevalence was 3.3%, with 0.08% due to Type 1 BrS and the rest from Types 2 and 3. In Denmark, the BrS prevalence was low at 0.001%. BrS affects men four times more than women and is more common in young adults than infants or children. BrS symptoms include SCD, syncope, palpitations, agonal breathing, and can be triggered by increased vagal tone, fever, and certain drugs like tricyclic antidepressants and alcohol.
BrS is associated with pre-excitation syndromes such as Wolff-Parkinson-White syndrome and supraventricular tachycardias such as atrioventricular nodal reentrant tachycardia, atrial flutter or fibrillation. It is also linked to sinus node dysfunction and conduction abnormalities such as reduced conduction velocity and blocks.
The diagnosis of BrS is based on a Type 1 ECG pattern with coved-shaped ST segment elevation ≥2 mm & negative T-wave in right precordial leads. It can also be diagnosed by converting a type 2 or type 3 ECG pattern to type 1 with drug challenge. The latest criteria exclude clinical findings, like history of VT/VF, in EPS. The Shanghai BrS Score assigns points based on ECG, clinical findings, family history & genetic results to classify as non-diagnostic, possible or probable/definite. ECG leads in 4th intercostal spaces may not be sensitive enough to detect BrS, but ST segment elevation is more pronounced in 2nd intercostal spaces.
BrS was once thought to be an autosomal dominant condition with inconsistent expression, but this has been proven false. The relationship between genetics and phenotype is unclear as not all affected family members carry the same mutation. Other genes besides SCN5A may also contribute to BrS. Some genetic variations that are thought to be harmful may not actually result in any symptoms. Care must be taken when informing patients of these results, as they may not have any clinical significance.