Brugada syndrome: in search of a genotype-phenotype relationship

The Brugada syndrome (BS) is an autosomal dominant inherited cardiac disease characterized by an electrocardiogram (ECG) with a varying degree of ST-segment elevation in the right precordial leads, and (non-)specific conduction disorders. Patients often present with (aborted) sudden cardiac death due to ventricular tachy-arrhythmias. In a minority of patients, mutations in the gene encoding the cardiac sodium channel (SCN5A) can be found. The Brugada syndrome is therefore considered to be an ion channel disease. Genetic heterogeneity has been demonstrated but other causally related genes await identification. A genotype-phenotype relationship in Brugada syndrome as in the long QT syndrome was until recently unknown. The first step towards the establishment of such a relationship seems to be the recent observation of more prevalent conduction abnormalities in patients with an SCN5A mutation. Further establishment of a genotype-phenotype relationship in Brugada syndrome may simplify genetic screening, increase our basic understanding of the pathophysiology of this disease and make a more accurate discussion of the disease possible. In this paper we discuss the possible phenotypical features which may be expected to be determined by differences in genotype in Brugada syndrome.