Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations

Abstract Background The characteristics of epilepsy in patients with Kabuki syndromewith KMT2D mutations (KABUK1) have not yet been well documented. This is the first review to explore this. Materials & methods We enrolled 14 patients with KABUK1, whose median age was 13.6 years (range = 4.1–21.3 years). Their medical records from October 1981 to May 2016 were retrospectively analyzed. Results Epilepsy was present in 5 (36%) patients. Four of these patients presented with nonsense mutationsand one with missense mutations. None presented with brain abnormalities. Four patients presented with annual or monthly focalseizures, of which three evolved to bilateral convulsive seizures. Median onset age of focalepilepsy was 11.8 years (range = 9.5–12.8 years). One presented with monthly myoclonic seizures from age 11.2, whose mother with no other KABUK1 features, had focalepilepsy. The cumulative incidenceof epilepsy related to KABUK1 up until age 13 was 45%. Interictal electroencephalogram revealed focalparoxysmal epileptiform discharges (in frontal, central, and parietal regions) in three patients, diffuse high- voltage spike-and- wavesin one patient, and normal sleep record in one patient. Myoclonic seizures were rapidly controlled by levetiracetam. In contrast, focalseizures were not controlled in the early period of antiepileptic therapy. Conclusion This long-term follow-up of patients with KABUK1 revealed a higher prevalence of epilepsy than previously reported. The age of epilepsy onset and rate of focalseizures evolving to bilateral convulsive seizures in KABUK1 were also higher than previously reported in patients with clinically diagnosed Kabuki syndrome. Although seizure outcome is reported to be favorable in Kabuki syndrome, focalseizures in patients with KABUK1 were not immediately responsive to medication.