Genetic biomarkers for the risk of seizures in long QT syndrome

Neurology. 2016 Oct 18;87(16):1660-1668. doi: 10.1212/WNL.0000000000003056. Epub 2016 Jul 27.


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 (QTc) 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, QTc duration, and sex were independent predictors of seizures. LQTS+ participants with seizures had significantly longer QTc 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.

MeSH terms

  • Adult
  • Cohort Studies
  • ERG1 Potassium Channel / genetics
  • Female
  • Follow-Up Studies
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • KCNQ1 Potassium Channel / genetics
  • Long QT Syndrome / complications*
  • Long QT Syndrome / epidemiology
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / therapy
  • Male
  • Mutation
  • Prevalence
  • Registries
  • Risk
  • Risk Factors
  • Seizures / complications*
  • Seizures / epidemiology
  • Seizures / genetics*
  • Seizures / therapy
  • Severity of Illness Index
  • Young Adult


  • ERG1 Potassium Channel
  • Genetic Markers
  • KCNH2 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human