Ventricular fibrillation with prominent early repolarization associated with a rare variant of KCNJ8/KATP channel.
BACKGROUND
Early repolarization in the inferolateral leads has been recently recognized as a frequent syndrome associated with idiopathic ventricular fibrillation (VF). We report the case of a patient presenting dramatic changes in the ECG in association with recurrent VF in whom a novel genetic variant has been identified.


METHODS
This young female (14 years) was resuscitated in 2001 following an episode of sudden death due to VF. All examinations including coronary angiogram with ergonovine injection, MRI, and flecainide or isoproterenol infusion were normal. The patient had multiple (>100) recurrences of VF unresponsive to beta-blockers, lidocaine/mexiletine, verapamil, and amiodarone. Recurrences of VF were associated with massive accentuation of the early repolarization pattern at times mimicking acute myocardial ischemia. Coronary angiography during an episode with 1.2 mV J/ST elevation was normal. Isoproterenol infusion acutely suppressed electrical storms, while quinidine eliminated all recurrences of VF and restored a normal ECG over a follow-up of 65 months. Genomic DNA sequencing of K(ATP) channel genes showed missense variant in exon 3 (NC_000012) of the KCNJ8 gene, a subunit of the K(ATP) channel, conferring predisposition to dramatic repolarization changes and ventricular vulnerability.
Haïssaguerre
Michel
M
Université Bordeaux, Bordeaux-Pessac, France. michel.haissaguerre@chu-bordeaux.fr
Chatel
Stéphanie
S
Sacher
Frederic
F
Weerasooriya
Rukshen
R
Probst
Vincent
V
Loussouarn
Gildas
G
Horlitz
Marc
M
Liersch
Ruedige
R
Schulze-Bahr
Eric
E
Wilde
Arthur
A
Kääb
Stefan
S
Koster
Joseph
J
Rudy
Yoram
Y
Le Marec
Hervé
H
Schott
Jean Jacques
JJ
D000293:Adolescent; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D054086:KATP Channels; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D014693:Ventricular Fibrillation / Q000175:diagnosis* / Q000235:genetics*
D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C117780:mitochondrial K(ATP) channel; C092520:uK-ATP-1 potassium channel