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Heart Rhythm. 2008 Nov;5(11):1567-74. doi: 10.1016/j.hrthm.2008.08.010. Epub 2008 Aug 17.

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.

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  • 1Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

BACKGROUND:

Mexiletine may protect patients with long QT syndrome (LQTS) type 3 from arrhythmias. However, we found an unusual in utero presentation of intermittent atrioventricular block and ventricular tachycardia (spontaneous or lidocaine-induced) in a fetus and his sibling with LQTS.

OBJECTIVE:

The purpose of this study was to investigate the underlying channelopathy and functional alteration.

METHODS:

Mutations were searched in KCNQ1, HERG, KCNE1, KCNE2, and SCN5A genes. In expressed mutants, whole-cell voltage clamp defined the electrophysiologic properties.

RESULTS:

Novel missense mutations involving hERG (F627L) at the pore region and SCN5A (R43Q) at the N-terminus were found in the proband and in family members with prolonged QT interval. In oocytes injected with mRNA encoding hERG/ F627L, almost zero K(+) currents were elicited. In coinjected oocytes, the currents were decreased to half. In tsA201 cells transfected with SCN5A/R43Q, although the baseline kinetics of the Na current were similar to wild type, lidocaine caused a unique hyperpolarizing shift of the activation and increased the availability of Na currents at resting voltages. Window currents were enhanced due to a right shift of steady-state inactivation. These electrophysiologic alterations after lidocaine may lead to the development of ventricular tachycardia.

CONCLUSION:

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.

PMID:
18848812
[PubMed - indexed for MEDLINE]
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