Brugada syndrome and sudden death: value of molecular post-mortem examination

Abstract

Sudden death of cardiac origin especially in young subjects can be related a genetic trait. One of these is Brugada
syndrome (BRS). In approximately 25% of cases, BRS is due to an abnormal sodium channel caused by a mutation of the SNC5A gene located on chromosome 3. This gene is involved in the reduction of the sodium current
density. In 75% of cases, BRS is caused by a mutation of the glycerol-3-phosphate dehydrogenase 1-like (GPD1-
L) gene resulting in alterations of the sodium current at the cell surface.
BRS is associated with a high risk of ventricular arrhythmias, which can lead to sudden death through ventricular fibrillation. The diagnosis of BRS is based on ADN extraction and the search for mutated genes encoding the
SCN5A subunit of sodium channel during post-mortem examination. The role of necropsy is to protect the life of
the patient’s offspring, forebears and siblings as much as possible.
The management of patients with BRS includes the implantation of a defibrillator in those with a history of nearsudden death. In these patients as well as those with a family history of BRS, programmed ventricular stimulation
is needed. If stimulation is positive, the implantation of a defibrillator is absolutely required. If stimulation is negative, it is recommended to closely follow those patients in whom treatment with drugs that inhibit the cellular
entry of sodium ions such as Ic class antiarrhythmics, local anesthetics except xylocaine and tricyclic antidepressants should be avoided. ECG monitoring and treatment with low dose quinidine are necessary in case of ECG
anomalies (augmented ST segment, right bundle branch block).