Key result
SCN5A mutations are found in approximately 20% of genotyped Brugada syndrome cases, though they may act as modifiers rather than direct causes due to low penetrance and phenotypic overlap.
SCN5A mutations are present in about 20% of genotyped Brugada syndrome patients and may function as disease modifiers rather than direct causes.
SCN5A testing warrants cautious interpretation in Brugada syndrome; leaves open the modifier role and need for prospective validation.
Brugada syndrome (BrS) is associated with the familial sudden death syndrome, and more than 10 genes have been reported as causative for or modifiers of BrS. All gene mutations are related to functional changes of inward sodium or calcium currents or outward potassium currents. SCN5A was the first gene known to be associated with BrS; it encodes the α‐subunit of the cardiac sodium channel. Approximately 20% of BrS patients in genotyped cases were found to carry SCN5A mutations. The frequency for other BrS‐associated gene mutations is so low that genotype–phenotype correlations for these genes have not been studied to the same extent as SCN5A ‐related BrS. In some families with SCN5A mutations, the penetrance of the mutations is low, and pathophysiological changes in the right ventricular outflow tract were reported in patients with SCN5A mutations. Furthermore, the phenotypes of SCN5A ‐related BrS can overlap with other phenotypes, including long QT and sick sinus syndrome, thereby suggesting that SCN5A mutations might be modifiers for BrS, but they do not direct cause BrS. Here, we summarize the genetic background of BrS, with a particular focus on recent progress in this field.
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Horie et al. (2013) conducted a review in Brugada syndrome. SCN5A mutations are found in approximately 20% of genotyped Brugada syndrome cases, though they may act as modifiers rather than direct causes due to low penetrance and phenotypic overlap.