Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation.
PURPOSE
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.


METHODS
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.


KEY FINDINGS
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.


SIGNIFICANCE
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.
['Kato|Mitsuhiro|M|', 'Yamagata|Takanori|T|', 'Kubota|Masaya|M|', 'Arai|Hiroshi|H|', 'Yamashita|Sumimasa|S|', 'Nakagawa|Taku|T|', 'Fujii|Takanari|T|', 'Sugai|Kenji|K|', 'Imai|Kaoru|K|', 'Uster|Tami|T|', 'Chitayat|David|D|', 'Weiss|Shelly|S|', 'Kashii|Hirofumi|H|', 'Kusano|Ryosuke|R|', 'Matsumoto|Ayumi|A|', 'Nakamura|Kazuyuki|K|', 'Oyazato|Yoshinobu|Y|', 'Maeno|Mari|M|', 'Nishiyama|Kiyomi|K|', 'Kodera|Hirofumi|H|', 'Nakashima|Mitsuko|M|', 'Tsurusaki|Yoshinori|Y|', 'Miyake|Noriko|N|', 'Saito|Kayoko|K|', 'Hayasaka|Kiyoshi|K|', 'Matsumoto|Naomichi|N|', 'Saitsu|Hirotomo|H|']
D004252:DNA Mutational Analysis D004569:Electroencephalography D004827:Epilepsy D005091:Exons D005260:Female D020022:Genetic Predisposition to Disease D005820:Genetic Testing D006801:Humans D007223:Infant D007231:Infant, Newborn D051658:KCNQ2 Potassium Channel D008279:Magnetic Resonance Imaging D008297:Male D009154:Mutation D014057:Tomography, X-Ray Computed
Early onset epileptic encephalopathy KCNQ2 Ohtahara syndrome Ion channel Mosaic