Abnormal expression of cardiac neural crest cells in heart development: A different hypothesis for the etiopathogenesis of Brugada syndrome

Abstract

R B A a m g e e m p t d t l ntroduction n 1992, the Brugada brothers described a new arrhythmoenic syndrome consisting of syncopal episodes or sudden eath caused by malignant ventricular tachyarrhythmias in atients devoid of clear-cut evidence of structural cardiac ompromise. In the most typical cases, patients showed a eculiar ECG pattern resembling right bundle branch block RBBB) together with ST-segment elevation and T-wave nversion in precordial leads V1–V3. 1 Approximately 20% f these patients were shown to have a genetic disorder due o mutations in the sodium channel gene SCN5A, with utosomal dominant transmission. The syndrome is the eading cause of natural death among young men, particuarly in southeast Asia. It is responsible for approximately % to 12% of all sudden deaths and at least 20% of sudden eaths occurring in individuals with apparently structural ormal hearts. The ECG abnormalities constitute the hallmarks of Bruada syndrome in the absence of any other conditions nown to induce similar QRS and ST-segment changes in he right precordial leads. Two main morphologies of STegment elevation usually can be recognized: type 1, which hows a coved ST-segment elevation, and type 2, which is haracterized by a saddleback appearance of the ST segent; both are accompanied by an atypical RBBB pattern. ubtle QT prolongation has been observed in some cases, as ave atrioventricular (AV) depolarization abnormalities, hich include a prolonged duration of the P wave, PR nterval, and QRS interval, particularly in patients linked to CN5A mutations. The spontaneous daily fluctuations ob-