Two Japanese cases of epileptic encephalopathy associated with an FGF12 mutation

Brain Dev. 2018 Sep;40(8):728-732. doi: 10.1016/j.braindev.2018.04.002. Epub 2018 Apr 23.


A heterozygous mutation in the fibroblast growth factor 12 (FGF12) gene, which elevates the voltage dependence of neuronal sodium channel fast inactivation, was recently identified in some patients with epileptic encephalopathy. Here we report 1 Japanese patient diagnosed with early infantile epileptic encephalopathy (EIEE) and another diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). These 2 patients had an identical heterozygous missense mutation [c.341G>A:p.(Arg114His)] in FGF12 , which was identified with whole-exome sequencing. This mutation is identical to previously reported mutations in cases with early onset epileptic encephalopathy. One of our cases exhibited EIMFS, and this case responded to phenytoin and high-dose phenobarbital (PB). FGF12-related epileptic encephalopathy may exhibit diverse phenotypes and may respond to sodium channel blockers or high-dose PB.

Keywords: Early onset epileptic encephalopathy (EIEE); Epilepsy of infancy with migrating focal seizures (EIMFS); FGF12; High-dose phenobarbital; Parental mosaicism.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / physiopathology
  • Epilepsies, Partial / diagnostic imaging
  • Epilepsies, Partial / drug therapy
  • Epilepsies, Partial / genetics*
  • Epilepsies, Partial / physiopathology
  • Fibroblast Growth Factors / genetics*
  • Humans
  • Infant
  • Male
  • Mutation, Missense*
  • Phenotype
  • Spasms, Infantile / diagnostic imaging
  • Spasms, Infantile / drug therapy
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology


  • FGF12 protein, human
  • Fibroblast Growth Factors

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy