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At a glance

A familial disorder characterized by spontaneous idiopathic ventricular fibrillation that probably is one of the most frequent causes of sudden death in patients with a structurally normal heart.

Synonyms

Idiopathic Ventricular Fibrillation; Right Bundle Branch Block, ST-Segment Elevation, and Sudden Death Syndrome; Sudden Unexplained Nocturnal Death Syndrome. Due to the relatively high incidence of the disease in South-Asia, many countries/languages have their own names for the disorder, eg, “bangungut” or “urom” (Philippines), “non lai tai” (Laos), “lai-tai” (Thailand), “dolyeonsa” (Korea), “digeuton” (Indonesia), “bei gui ya” (China) and “pokkuri” (Japan).

History

The disease bears the names of the two Spanish physicians and brothers Pedro and Josep Brugada, who in 1992 described eight patients with episodes of aborted sudden death. However, the disease had been described before.

Incidence

The prevalence is estimated to be 1 to 5:10,000 in the general population in Western countries. A higher frequency is found in Asian and Southeast Asian countries (eg, Thailand, Philippines, and Japan where its prevalence is up to 12:10,000). Approximately three quarters of clinically affected individuals are males, but the risks and outcome are equal in both affected genders.

Genetic inheritance

Autosomal dominant. The only exception is BrS 6 (see below), which is caused by mutations in the KCNE5-gene and associated with X-linked inheritance. The vast majority of patients with BrS already have an affected parent and the proportion of de novo mutations is considered to be around 1%. To date, at least 23 different genes with over 300 different mutations have been linked to BrS, and genetic abnormalities are found in up to 50% of genotyped patients with BrS. The most common mutations involve the SCN5A gene (Sodium voltage-gated channel alpha subunit 5), which encodes the alpha-subunit of the cardiac sodium channel (that is responsible for the fast sodium influx in phase 0 of the cardiac action potential) and are found in up to 28% of genotype positive patients and define the genetic BrS 1. These mutations have been mapped to chromosome 3p22.2. Mutations in the SCN10A gene (BrS 17), also located on chromosome 3p22.2, account for approximately 16% of BrS patients. The different genetic types of BrS are determined by the underlying mutations with the most common forms listed below. All other types are significantly rarer than BrS 1 and 17 (BrS 3 in 6.6%, BrS 4 in 4.8%, BrS 5 in 1.1.%, BrS 8 in 2%, and BrS 9 in 1.8%, all others account for < 1% each of patients). Please note that the genetic types of BrS are different from the clinical types BrS 1 and 2, which are based on the ECG findings.

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BrS Type Mutated gene Encoded protein Location
BrS 1 SCN5A Sodium voltage-gated channel alpha subunit 5 3p22.2
BrS 2 GPD1L Glycerol-3-phosphate dehydrogenase 1-like protein 3p22.3
BrS 3 CACNA1C Calcium voltage-gated channel subunit alpha1 C 12p13.33
BrS 4 CACNB2 Calcium voltage-gated channel auxiliary subunit beta ...

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