Neuropediatrics 2015; 46(04): 287-291
DOI: 10.1055/s-0035-1554098
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

SYNGAP1 Mutation in Focal and Generalized Epilepsy: A Literature Overview and A Case Report with Special Aspects of the EEG

Celina von Stülpnagel1, 2, Claudia Funke3, Caroline Haberl4, Konstanze Hörtnagel3, Jerome Jüngling3, Yvonne G. Weber5, Martin Staudt1, 6, Gerhard Kluger1, 2
  • 1Hospital for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany
  • 2Paracelsus Medical University Salzburg, Salzburg, Austria
  • 3CEGAT GmbH, Tübingen, Germany
  • 4Praxis für Neuropädiatrie, Starnberg, Germany
  • 5Department for Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tübingen, Germany
  • 6Department for Neuropediatrics and Developmental Neurology, University Hospital for Children and Adolescents, Tübingen, Germany
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05. November 2014

09. März 2015

25.Juni 2015 (eFirst)


BackgroundSYNGAP1, 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.

Patient 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.

Discussion 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.