SCN5A variants can be associated with overlapping phenotypes such as Brugada syndrome (BrS), sinus node dysfunction and supraventricular tachyarrhythmias.
We resequenced the core promoter region of SCN5A and the regulatory regions of SCN5A transcription in 1298 patients with arrhythmia phenotypes (atrial fibrillation, n=444; sinus node dysfunction, n=49; conduction disease, n=133; Brugada syndrome, n=583; and idiopathic ventricular fibrillation, n=89).
We identified an SCN5A mutation in a patient with sinus node dysfunction and epinephrine-induced QT prolongation, which was an atypical phenotype for LQT3.
Phenotypic overlap of type 3 long QT syndrome (LQT3), Brugada syndrome (BrS), cardiac conduction disease (CCD), and sinus node dysfunction (SND) is observed with SCN5A mutations.
The spectrum of phenotypes related to mutations of the SCN5A gene include Brugada syndrome (BS), long QT syndrome, progressive cardiac conduction defect, and sinus node disease (SND).
We explored the interacting effects of Scn5a disruption and aging on the pathogenesis of sinus node dysfunction in a heterozygous Scn5a knockout (Scn5a(+/-)) mouse model.
Variations in the gene encoding for the major sodium channel (Na(v)1.5) in the heart, SCN5A, has been shown to cause a number of arrhythmia syndromes (with or without structural changes in the myocardium), including the long-QT syndrome (type 3), Brugada syndrome, (progressive) cardiac conduction disease, sinus node dysfunction, atrial fibrillation, atrial standstill, and dilated cardiomyopathy.
To date, mutational analyses have revealed more than 200 distinct mutations in SCN5A, of which at least 20 mutations are associated with sinus node dysfunction including SSS.
Mutations in the cardiac sodium channel gene SCN5A are responsible for a spectrum of hereditary arrhythmias, including type-3 long QT syndrome (LQT3), Brugada syndrome (BrS), conduction disturbance and sinus node dysfunction.