Does age affect response to quinidine in patients with KCNT1 mutations? Report of three new cases and review of the literature

Purpose: Gain-of-function mutations in the KCNT1 gene have been reported in a number of drug resistant epilepsy syndromes including Epilepsy of Infancy with Migrating Focal Seizures. Quinidine, a potassium channel blocker, has been proposed as a potential therapeutic agent with only a few patients reported in the literature to have received it. Here we report 3 additional children, with such KCNT1 mutations and refractory seizures, who received quinidine therapy.

Methods: Retrospective chart review of 3 children with KCNT1 mutations, of ages 3 months, 9 years and 13 years old. Video-EEG documented seizure type and frequency. Seizure frequency was compared before and after quinidine initiation. We then analyzed seizure response (defined as > 50% reduction in seizure frequency) as it related to age in our 3 reported children, an additional 2 previously seen by us in our center, and an additional 3 reported in the literature (total 8 cases).

Results: In our report, the 3-month-old infant responded to quinidine, while the two older children did not. Using a cutoff of 4 years of age, review of the total of 8 cases, five from our center, revealed that all patients younger than 4 years responded to quinidine (4/4), while none of the ones older than 4 years did (0/4).

Conclusion: The above-mentioned findings support performance of prospective controlled studies of quinidine efficacy in children with KCNT1 gain-of-function mutations that control for age as a possible variable affecting response.