Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome

Am J Med Genet A. 2007 Jul 1;143A(13):1481-8. doi: 10.1002/ajmg.a.31819.


Cardio-facio-cutaneous syndrome (CFC) and Costello syndrome (CS) are disorders with an overlapping spectrum of congenital anomalies. Mutations in the RAS-MAPK pathway have recently been reported in both of these syndromes, with HRAS mutations characteristic for CS and BRAF and MEK1/2 mutations for CFC. We report on a 3-year-old boy who underwent a cardiac transplant at age 8 months for hypertrophic cardiomyopathy; he was subsequently suspected to have CS. At age 35 months he presented with an intra-cardiac mass that was diagnosed as metastatic hepatoblastoma. Although hepatoblastoma is not known to have an increased frequency in immunocompromised patients, questions were raised as whether the post-transplant immuno-suppressive therapy played a role in tumor development. The patient died shortly thereafter and his post-mortem DNA analysis revealed a MEK1 mutation (Y130C) previously reported in CFC. While CS is associated with increased cancer risk, only a single case of leukemia has been reported in a patient with CFC, making this the first case of a solid tumor reported in a patient with CFC.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Abnormalities, Multiple* / diagnosis
  • Abnormalities, Multiple* / genetics
  • Abnormalities, Multiple* / pathology
  • Child, Preschool
  • Face / abnormalities*
  • Fatal Outcome
  • Heart Defects, Congenital / complications*
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / surgery
  • Heart Transplantation*
  • Hepatoblastoma / etiology*
  • Hepatoblastoma / pathology
  • Humans
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / pathology
  • MAP Kinase Kinase 1 / genetics
  • Male
  • Mutation
  • Skin Abnormalities / complications*
  • Skin Abnormalities / genetics
  • Syndrome


  • MAP Kinase Kinase 1