A Novel SCN5A Mutation in a Patient with Coexistence of Brugada Syndrome Traits and Ischaemic Heart Disease

Abstract

Brugada syndrome (BrS) is a primary electrical heart disease, which can lead to sudden cardiac death. In older patients with BrS, the disease may coexist with ischaemic heart disease (IHD) and recent studies support a synergistic proarrhythmic effect of the two disease entities. We report a case that illustrates this. The index patient was a middle-aged patient with BrS traits, IHD, and aborted sudden cardiac death. Mutation analysis discovered a novel mutation P468L in the Na(V)1.5 sodium channel. Surprisingly, voltage-clamp experiments on the wild-type and mutant Na(V)1.5 channels expressed in HEK cells revealed no functional effect of the mutation. In a patient like ours, the distinction between IHD and BrS as the cause of an aborted sudden cardiac death is hard to establish and mounting evidence shows that coexistence of the two may have a synergistic proarrhythmic effect.

Figure 1

ECG (paper speed 25 mm/s) taken just after the patient was resuscitated. Notice the type-1 BrS configuration in V₁ (upper arrow) and the type 2 configuration in V₂ (lower arrow). All recordings were taken from the same ECG.

Figure 2

The family pedigree: the proband (II:1) is marked with an arrow.