Familial cardiofaciocutaneous syndrome in a father and a son with a novel MEK2 mutation

Am J Med Genet A. 2015 Feb;167A(2):385-8. doi: 10.1002/ajmg.a.36429. Epub 2014 Dec 8.


Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the group of RASopathies. It is typically characterized by congenital heart defects, short stature, dysmorphic craniofacial features, intellectual disability, failure to thrive, and ectodermal abnormalities such as hyperkeratosis and sparse, brittle, curly hair. CFC syndrome is caused by dominant mutations in one of the four genes BRAF, MEK1, MEK2, and KRAS. Only three familial cases of CFC syndrome have been reported to date, whereas the vast majorities are sporadic cases due to de novo mutations. We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene. This observation further documents the possibility of vertical transmission of CFC syndrome, which appears to be associated with rare mutations and relatively mild intellectual disability in affected individual. The hypomorphic effect of specific mutations particularly regarding neurocognitive issues may be related to the variable fertility of affected individuals.

Keywords: RASopathy; autosomal dominant; congenital heart defect; mental retardation; mutation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Ectodermal Dysplasia / diagnosis*
  • Ectodermal Dysplasia / genetics*
  • Exons
  • Facies
  • Failure to Thrive / diagnosis*
  • Failure to Thrive / genetics*
  • Genetic Association Studies
  • Heart Defects, Congenital / diagnosis*
  • Heart Defects, Congenital / genetics*
  • Heterozygote
  • Humans
  • Infant
  • MAP Kinase Kinase 2 / genetics*
  • Male
  • Mutation*
  • Phenotype


  • MAP Kinase Kinase 2

Supplementary concepts

  • Cardiofaciocutaneous syndrome