Early onset epileptic encephalopathy caused by novel compound heterozygous mutation of WWOX gene

Int J Dev Neurosci. 2020 Apr;80(2):157-161. doi: 10.1002/jdn.10013. Epub 2020 Feb 25.


The human WW domain containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene. However, recent reports have demonstrated its dominant role in autosomal recessive disorders of the central nervous system, especially in early onset epileptic encephalopathy. Here, we report a Chinese case with novel compound heterozygous mutation of WWOX gene (c.229_230+2del mutation originated from her mother and c.1065dup (p.Ala356Serfs*173) variation from her father), and compare them to previously reported 59 WWOX-related epileptic encephalopathy (WOREE). Early onset and frequent epileptic seizures in the postnatal period, hypsarrhythmia patterns in EEG background and retarded development are the most important characteristics of WOREE in infants. Although the seizures in our case can be controlled by phenobarbital and topiramate, the prognosis of WOREE is poor.

Keywords: early onset epileptic encephalopathy; oxidoreductase containing WW domain.

Publication types

  • Case Reports

MeSH terms

  • Anticonvulsants / therapeutic use
  • Brain Diseases / drug therapy
  • Brain Diseases / etiology
  • Brain Diseases / genetics*
  • Electroencephalography
  • Epilepsy / complications
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Female
  • Heterozygote
  • Humans
  • Infant
  • Intellectual Disability / genetics
  • Mutation / genetics
  • Prognosis
  • Spasms, Infantile / drug therapy
  • Spasms, Infantile / genetics
  • Tumor Suppressor Proteins / genetics*
  • WW Domain-Containing Oxidoreductase / genetics*


  • Anticonvulsants
  • Tumor Suppressor Proteins
  • WW Domain-Containing Oxidoreductase
  • WWOX protein, human