In utero onset of long QT syndrome with atrioventricular block and spontaneous or lidocaine-induced ventricular tachycardia: Compound effects of hERG pore region mutation and SCN5A N-terminus variant

Abstract

We identified a novel hERG/F627L mutation that results in LQTS with fetal onset of atrioventricular block and ventricular tachycardia. A coexisting SCN5A/R43Q variant, although it per se does not prolong repolarization, contributes to the development of ventricular tachyarrhythmias after lidocaine. Patients with such latent lidocaine-induced phenotype who are given lidocaine or mexiletine may be at risk.

Primary ventricular tachycardia in paediatric population in a tertiary centre

“…Among the three patients with fetal onset of VT, a novel SCN5A mutation was identified in one patient,5 and a compound SCN5A and KCNH2 mutation was identified in another patient 6…”

Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus

“…For lidocaine, these candidates comprise KCNA1 and KCNC1, plus KCNH2 [37,38], which has also been implicated in phenytoin effects [39]. …”

Drug-Induced Arrhythmia

“…Recently, a mutation in SCN5A has been described that predisposes to ventricular tachycardia in the presence of class I drugs such as lidocaine. 67 The vast majority of patients receiving antiarrhythmic drugs that act predominantly through sodium channel blockade are selected on the basis of a low-risk profile for proarrhythmia (eg, absence of ischemic or other structural heart disease) and are generally monitored with routine ECGs, which are likely to detect evidence of excessive sodium channel blockade, manifest as widening of the QRS complex. In contrast, patients treated with noncardiac drugs that have sodium channel-blocking properties are less likely to have such screening.…”