Epilepsy in RAS/MAPK syndrome: two cases of cardio-facio-cutaneous syndrome with epileptic encephalopathy and a literature review

Seizure. 2012 Jan;21(1):55-60. doi: 10.1016/j.seizure.2011.07.013. Epub 2011 Aug 25.


We report two individual cases of cardio-facio-cutaneous (CFC) syndrome with severe neurological impairment consisting of infantile spasms with hypsarrhythmia and refractory epilepsy with multifocal epileptic paroxysms such as modified hypsarrhythmia. Both cases shared diffuse brain atrophy and severely delayed myelination on neuroimaging. Genetic analysis revealed individual heterozygous mutations in the KRAS (phenotype of CFC/Noonan syndrome) and BRAF genes (phenotype of CFC syndrome). Neurological impairment in cases with mutations in the RAS/MAPK (mitogen activated protein kinase) signal pathway may be more severe, and could be linked to some forms of refractory epilepsy, especially epileptic encephalopathy that includes infantile spasms.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Atrophy
  • Brain Diseases / etiology
  • Brain Diseases / physiopathology
  • Child, Preschool
  • Ectodermal Dysplasia / complications*
  • Ectodermal Dysplasia / genetics*
  • Ectodermal Dysplasia / physiopathology
  • Epilepsy / etiology*
  • Epilepsy / physiopathology
  • Facies
  • Failure to Thrive / complications*
  • Failure to Thrive / genetics*
  • Failure to Thrive / physiopathology
  • Female
  • Heart Defects, Congenital / complications*
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / physiopathology
  • Humans
  • Infant, Newborn
  • Male
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Signal Transduction / physiology
  • ras Proteins / genetics*


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins

Supplementary concepts

  • Cardiofaciocutaneous syndrome