title: Episodic tremors representing cortical myoclonus are characteristic in Angelman syndrome due to UBE3A mutations.
abstract: OBJECTIVE
  Neurological manifestations including psychomotor developmental delay and epilepsy in patients with Angelman syndrome caused by ubiquitin protein ligase E3A (UBE3A) mutations has been considered similar but is relatively milder than that in patients with deletion-type Angelman syndrome. This makes the diagnosis of the former subgroup often difficult. We here characterized epilepsy, specifically the types of tremulous movement, in 4 patients (age, 3-38years) with Angelman syndrome caused by UBE3A mutations.
  
  
  METHODS
  Ictal electroencephalography was used to record episodic tremors in all study patients. Jerk-locked averaging was performed using digital electroencephalography and surface electromyogram data from patients who were monitored for 24h.
  
  
  RESULTS
  All patients had tremors in the limbs, head, and trunk, which resulted in 2 patients falling backward. These tremors lasted several seconds, and could emerge in clusters for hours in older patients. In addition, the tremors coincided with 7-8Hz rhythmic activity with a frontocentral predominance, diffuse spike-wave bursts, or no apparent change on electroencephalography. In 2 patients, these tremors were confirmed as cortical myoclonus using jerk-locked averaging. The other seizure types were isolated generalized myoclonus and tonic seizures. None of the patients experienced atypical absence seizures. Levetiracetam therapy was effective in controlling the myoclonic events in 2 of the 3 patients.
  
  
  CONCLUSIONS
  Semirhythmic myoclonus is common in patients with Angelman syndrome caused by UBE3A mutations, and such myoclonic events are often life disabling. The preserved expression of gamma-aminobutyric acid type A receptor subunit genes located proximal to UBE3A might explain the low prevalence of absence seizures in this population.
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan. Electronic address: masapon.go@gmail.com.
authors.forename: Masahide
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Honda
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Miyatake
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Takeshita
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishiyama
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Komaki
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakagawa
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Pediatrics, Isawa-Kyoritu Hospital, Yamanashi, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Uto
authors.affiliation: Division of Neurology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Department of Pediatrics, Uwajima City Hospital, Ehime, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Motoki
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
mesh_terms: D000293:Adolescent; D000328:Adult; D017204:Angelman Syndrome / Q000150:complications* / Q000235:genetics*; D058256:Brain Waves / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009207:Myoclonus / Q000209:etiology*; D014202:Tremor / Q000209:etiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Jerk-locked averaging; Levetiracetam; Myoclonic absence; Tremor; UBE3A mutations