title: Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations.
abstract: BACKGROUND
  The characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations (KABUK1) have not yet been well documented. This is the first review to explore this.
  
  
  METHODS
  We enrolled 14 patients with KABUK1, whose median age was 13.6years (range=4.1-21.3years). 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 mutations and one with missense mutations. None presented with brain abnormalities. Four patients presented with annual or monthly focal seizures, of which three evolved to bilateral convulsive seizures. Median onset age of focal epilepsy was 11.8years (range=9.5-12.8years). One presented with monthly myoclonic seizures from age 11.2, whose mother with no other KABUK1 features, had focal epilepsy. The cumulative incidence of epilepsy related to KABUK1 up until age 13 was 45%. Interictal electroencephalogram revealed focal paroxysmal epileptiform discharges (in frontal, central, and parietal regions) in three patients, diffuse high-voltage spike-and-waves in one patient, and normal sleep record in one patient. Myoclonic seizures were rapidly controlled by levetiracetam. In contrast, focal seizures were not controlled in the early period of antiepileptic therapy.
  
  
  CONCLUSIONS
  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 focal seizures 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, focal seizures in patients with KABUK1 were not immediately responsive to medication.
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Japan. Electronic address: hayashi@aichi-colony.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kurahashi
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Pediatrics, Aichi Prefectural Colony Central Hospital, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Koshimizu
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Japan; Department of Pediatrics, Aichi Medical University, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Natsume
authors.affiliation: Department of Neurology, Aichi Children's Health and Medical Center, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Functioning Science, Institute for Developmental Research, Aichi Human Service Center, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Aichi Prefectural Colony Central Hospital, Japan; Department of Pediatrics, Nagoya Central Care Center for Disabled Children, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Taniai
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Maki
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Abe-Hatano
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatric Neurology, Aichi Prefectural Colony Central Hospital, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000015:Abnormalities, Multiple / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D000293:Adolescent; D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D005145:Face / Q000002:abnormalities* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D015837:Vestibular Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins
keywords: Cumulative incidence; Electroencephalogram; KABUK1; Seizure