title: Leukemia in Cardio-facio-cutaneous (CFC) syndrome: a patient with a germline mutation in BRAF proto-oncogene.
abstract: 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.
authors.affiliation: Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Narumi
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002648:Child; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D020732:Cytogenetic Analysis / Q000379:methods; D005145:Face / Q000002:abnormalities; D018095:Germ-Line Mutation / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D012868:Skin Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D013577:Syndrome
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf