title: Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arai
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Yamashita
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Takanari
authors.initials: T
authors.lastname: Fujii
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.forename: Kaoru
authors.initials: K
authors.lastname: Imai
authors.forename: Tami
authors.initials: T
authors.lastname: Uster
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Shelly
authors.initials: S
authors.lastname: Weiss
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kashii
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kusano
authors.forename: Ayumi
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Oyazato
authors.forename: Mari
authors.initials: M
authors.lastname: Maeno
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kodera
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
mesh_terms: D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human
keywords: Early onset epileptic encephalopathy; Ion channel; KCNQ2; Mosaic; Ohtahara syndrome