title: SYNGAP1 Mutation in Focal and Generalized Epilepsy: A Literature Overview and A Case Report with Special Aspects of the EEG.
abstract: BACKGROUND
  SYNGAP1, which encodes a RAS-GTPase-activating protein, is located on the short arm of chromosome 6. Heterozygous SYNGAP1 gene mutations have been associated with autism spectrum disorders, delay of psychomotor development, acquired microcephaly, and several forms of idiopathic generalized epilepsy. Here, we report a patient with a new SYNGAP1 stop mutation, and compare the phenotype with published cases with SYNGAP1 mutations and epilepsy.
  
  
  METHODS
  This 15-year-old nondysmorphic girl with intellectual disability developed drop attacks at the age of 2 years, later clonic and clonic-tonic as well as myoclonic seizures predominantly during sleep. The epilepsy was well-controlled by valproic acid (VPA) and later on with levetiracetam. Electroencephalogram (EEG) showed a complete EEG-normalization with eye opening as well as photosensitivity. Magnetic resonance imaging was normal. Genetic analysis revealed a de novo heterozygous stop mutation (c.348C>A, p.Y116*) in exon 4 of the SYNGAP1 gene.
  
  
  CONCLUSIONS
  The main clinical features of our patient (i.e., intellectual disability and idiopathic epilepsy) are compatible with previous reports on patients with SYNGAP1 mutations. The unusual feature of complete EEG normalization with eye opening has not been reported yet for this genetic abnormality. Furthermore, our case provides further support for efficacy of VPA in patients with SYNGAP1 mutation-related epilepsy.
authors.affiliation: Hospital for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany.
authors.forename: Celina
authors.initials: C
authors.lastname: von Stülpnagel
authors.affiliation: CEGAT GmbH, Tübingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Funke
authors.affiliation: Praxis für Neuropädiatrie, Starnberg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Haberl
authors.affiliation: CEGAT GmbH, Tübingen, Germany.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Hörtnagel
authors.affiliation: CEGAT GmbH, Tübingen, Germany.
authors.forename: Jerome
authors.initials: J
authors.lastname: Jüngling
authors.affiliation: Department for Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Weber
authors.affiliation: Hospital for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Staudt
authors.affiliation: Hospital for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kluger
mesh_terms: D000293:Adolescent; D001921:Brain / Q000503:physiopathology; D004828:Epilepsies, Partial / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: C484739:SYNGAP1 protein, human; D020703:ras GTPase-Activating Proteins