Genetic seizure susceptibility underlying acute encephalopathies in childhood

Epilepsy Res. 2010 Oct;91(2-3):143-52. doi: 10.1016/j.eplepsyres.2010.07.005. Epub 2010 Aug 2.


We herein investigated risk factors of pediatric acute encephalopathy (AE) regarding the hitherto uncharacterized genetic background of seizure susceptibility underlying the pathogenesis of AE. The study included 15 patients with a history of various types of AE in childhood. We undertook the mutational analysis of the neuronal sodium channel alpha 1 subunit (SCN1A) gene which is the most representative gene for hyperthermia-induced seizure susceptibility. Six patients (40%) had a positive family history of seizures or AE, especially febrile seizures, in first- or second-degree relatives. The SCN1A-R1575C mutation was detected in a patient with a history of acute encephalitis with refractory, repetitive partial seizures (AERRPS) and also in the patient's apparently healthy father. In the present study, dense familial seizure predisposition was present in the patients with AE. Although the presence of seizure susceptibility alone is insufficient to cause AE, it can exacerbate seizures and the subsequent development of inflammatory reactions in the brain when environmental factors are included. Genetic seizure susceptibility may contribute to some types of AE in childhood.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Infant
  • Intellectual Disability / etiology
  • Intellectual Disability / genetics
  • Intellectual Disability / physiopathology
  • Lennox Gastaut Syndrome
  • Male
  • Molecular Sequence Data
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Seizures / etiology
  • Seizures / genetics*
  • Seizures / physiopathology
  • Sodium Channels / genetics*
  • Spasms, Infantile / etiology
  • Spasms, Infantile / genetics
  • Spasms, Infantile / physiopathology
  • Young Adult


  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • SCN1A protein, human
  • Sodium Channels

Supplementary concepts

  • Epileptic encephalopathy, Lennox-Gastaut type