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Disease summary:
Brugada syndrome (BrS) was described in 1992. It is characterized by the presence of a typical electrocardiographic (ECG) pattern (right bundle branch block and persistent ST-segment elevation in right precordial leads) and it is associated with sudden cardiac death (SCD). To date, it is supposed to be responsible for 4% to 12% of total SCD cases, and 20% of SCD in patients with structurally normal hearts. The prevalence of the disease is difficult to estimate because the pattern is not always recognized or because it may transiently normalize. Nevertheless it is believed to be in the range of 1 to 5 in 10,000, being higher in Southeast Asia where the disease occurs endemically. The average age of diagnosis is usually around age 40, however, there has been description of affected individuals from age 1 to 84, and is more common in males than in females (8:1). BrS has also been described as responsible for sudden infant death syndrome (SIDS).
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Hereditary basis:
The BrS is a familial disease inherited with an autosomal dominant pattern of transmission and variable penetrance. In up to 60% of patients the disease can be sporadic, that is, absent in parents and other relatives. The BrS was classified as genetically determined with the identification in 1998 of the first mutations in SCN5A. Since then, more than 200 BrS-associated mutations have been described in SCN5A. Conversely, though, only 15% to 30% of patients with the clinical phenotype currently have a causative mutation identified at the SCN5A locus. Other 15 genes have been associated to BrS but with minor incidence: GPD1L, SCN1B, SCN2B, SCN3B, RANGRF, SLMAP, KCNE3, KCNj8, HCN4, KCNE5, KCND3, CACNA1C, CACNB2B, CACNA2D1, and TRPM4.
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Differential diagnosis:
The ECG pattern is the sine qua non of BrS diagnosis. Of importance is the fact that the specific morphology of the precordial QRST pattern is critical for establishing the diagnosis of the syndrome. Only the type 1 ECG pattern—J-point elevation of greater than 2 mm with a coved (downward convex) ST segment—is diagnostic of BrS, with type 2 and type 3 “saddleback” patterns being less specific.
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Diagnostic Criteria and Clinical Characteristics
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Sometimes, the diagnosis of BrS is difficult because of incomplete penetrance and dynamic ECG manifestations. Three repolarization patterns have been described: (a) type-1 ECG pattern, in which a coved ST-segment elevation greater than or equal to 2 mm is followed by a negative T wave, with little or no isoelectric separation, being this feature present in greater than one right precordial lead (from V1-V3); (b) type-2 ECG pattern, also characterized by a ST-segment elevation but followed by a positive or biphasic T wave that results in a saddle back configuration; (c) type-3 ECG pattern, a right precordial ST-segment elevation less than or equal to 1 mm either with a coved-type or a saddle-back ...