title: Epilepsy in RAS/MAPK syndrome: two cases of cardio-facio-cutaneous syndrome with epileptic encephalopathy and a literature review.
abstract: 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.
authors.affiliation: Department of Pediatrics, Kakogawa Hospital Organization, Kakogawa West-City Hospital, 384-1 Hiratsu, Yoneda-cho, Kakogawa, Hyogo 675-8611, Japan. ama-p@rc4.so-net.ne.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Adachi
authors.forename: Yu
authors.initials: Y
authors.lastname: Abe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
mesh_terms: D001284:Atrophy; D001927:Brain Diseases / Q000209:etiology / Q000503:physiopathology; D002675:Child, Preschool; D004476:Ectodermal Dysplasia / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D004827:Epilepsy / Q000209:etiology* / Q000503:physiopathology; D019066:Facies; D005183:Failure to Thrive / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000502:physiology; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins