Leukemia in Cardio-facio-cutaneous (CFC) syndrome: a patient with a germline mutation in BRAF proto-oncogene

J Pediatr Hematol Oncol. 2007 May;29(5):287-90. doi: 10.1097/MPH.0b013e3180547136.


Cardio-facio-cutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by a distinctive facial appearance, ectodermal abnormalities, and heart defects. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are caused by mutations in 2 genes that encode molecules of the RAS/MAPK (mitogen activated protein kinase) pathway (PTPN11 and HRAS, respectively). Recently, mutations in KRAS, BRAF, and MEK1/2 have been identified in patients with CFC syndrome. Somatic mutations in KRAS and BRAF have been identified in various tumors. In contrast, the association with malignancy has not been noticed in CFC syndrome. Here we report a 9-year-old boy diagnosed with CFC syndrome and acute lymphoblastic leukemia. Sequencing analysis of the entire coding region of KRAS and BRAF showed a de novo germline BRAF E501G (1502A-->G) mutation. Molecular diagnosis and careful observations should be considered in children with CFC syndrome because they have germline mutations in proto-oncogenes and might develop malignancy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / therapy
  • Child
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / therapy
  • Cytogenetic Analysis / methods
  • Face / abnormalities
  • Germ-Line Mutation / genetics*
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / therapy
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics
  • Intellectual Disability / therapy
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sequence Analysis, DNA / methods
  • Skin Abnormalities / diagnosis
  • Skin Abnormalities / genetics*
  • Skin Abnormalities / therapy
  • Syndrome


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf