Genetic biomarkers for the risk of seizures in long QT syndrome.

OBJECTIVES

The coprevalence, severity, and biomarkers for seizures and arrhythmias in long QT syndrome (LQTS) remain incompletely understood.

METHODS

Using the Rochester-based LQTS Registry, this study included large cohorts of LQTS1-3 participants (LQTS, n = 965) and those without a LQTS mutation (LQTS, n = 936).

RESULTS

Compared to LQTS participants, there was a higher prevalence of LQTS1, LQTS2, and LQTS participants classified as having seizures (p < 0.001, i.e., history of seizures/epilepsy or antiseizure medication). LQTS participants with longer corrected QT interval (QT) durations were more likely to have seizures. LQTS2 mutations in the KCNH2 pore domain were positive predictors for both arrhythmias and seizures. In contrast, mutations in the cyclic nucleotide binding domain (cNBD) of KCNH2 conferred a negative risk of seizures, but not arrhythmias. LQTS2, KCNH2-pore, KCNH2-cNBD, QT duration, and sex were independent predictors of seizures. LQTS participants with seizures had significantly longer QT durations, and a history of seizures was the strongest independent predictor of arrhythmias (hazard ratio 4.09, 95% confidence interval 2.63-6.36, p < 0.001).

CONCLUSIONS

This study highlights potential biomarkers for neurocardiac electrical abnormalities in LQTS.