Full-Length Original Research
Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation
Article first published online: 26 APR 2013
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
Volume 54, Issue 7, pages 1282–1287, July 2013
How to Cite
Kato, M., Yamagata, T., Kubota, M., Arai, H., Yamashita, S., Nakagawa, T., FujII, T., Sugai, K., Imai, K., Uster, T., Chitayat, D., Weiss, S., Kashii, H., Kusano, R., Matsumoto, A., Nakamura, K., Oyazato, Y., Maeno, M., Nishiyama, K., Kodera, H., Nakashima, M., Tsurusaki, Y., Miyake, N., Saito, K., Hayasaka, K., Matsumoto, N. and Saitsu, H. (2013), Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia, 54: 1282–1287. doi: 10.1111/epi.12200
- Issue published online: 1 JUL 2013
- Article first published online: 26 APR 2013
- Manuscript Accepted: 18 MAR 2013
- Ministry of Health, Labour and Welfare of Japan. Grant Numbers: 24133701, 11103577, 11103340, 10103235
- Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science. Grant Number: 24591500
- Japan Society for the Promotion of Science. Grant Numbers: 10013428, 12020465
- Takeda Science Foundation
- the Japan Science and Technology Agency
- the Strategic Research Program for Brain Sciences. Grant Number: 11105137
- Ministry of Education, Culture, Sports, Science and Technology of Japa. Grant Number: 12024421
- KCNQ2 ;
- Ohtahara syndrome;
- Early onset epileptic encephalopathy;
- Ion channel
KCNQ2 mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy (EOEE). In this study, we aimed to delineate the clinical spectrum of EOEE associated with KCNQ2 mutation.
A total of 239 patients with EOEE, including 51 cases with Ohtahara syndrome and 104 cases with West syndrome, were analyzed by high-resolution melting (HRM) analysis or whole-exome sequencing. Detailed clinical information including electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were collected from patients with KCNQ2 mutation.
A total of nine de novo and one inherited mutations were identified (two mutations occurred recurrently). The initial seizures, which were mainly tonic seizures, occurred in the early neonatal period in all 12 patients. A suppression-burst pattern on EEG was found in most. Only three patients showed hypsarrhythmia on EEG; eight patients became seizure free when treated with carbamazepine, zonisamide, phenytoin, topiramate, or valproic acid. Although the seizures were relatively well controlled, moderate-to-profound intellectual disability was found in all except one patient who died at 3 months.
De novo KCNQ2 mutations are involved in EOEE, most of which cases were diagnosed as Ohtahara syndrome. These cases showed distinct features with early neonatal onset, tonic seizures, a suppression-burst EEG pattern, infrequent evolution to West syndrome, and good response to sodium channel blockers, but poor developmental prognosis. Genetic testing for KCNQ2 should be considered for patients with EOEE.