title: Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome.
abstract: 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.
authors.affiliation: Department of Pediatrics,University of Virginia Health System, Charlottesville, Virginia. almohama@mail.nih.gov
authors.forename: Mohamad M
authors.initials: MM
authors.lastname: Al-Rahawan
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Chute
authors.forename: Katia
authors.initials: K
authors.lastname: Sol-Church
authors.forename: Karen W
authors.initials: KW
authors.lastname: Gripp
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Stabley
authors.forename: Nancy L
authors.initials: NL
authors.lastname: McDaniel
authors.forename: William G
authors.initials: WG
authors.lastname: Wilson
authors.forename: Peter E
authors.initials: PE
authors.lastname: Waldron
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002675:Child, Preschool; D005145:Face / Q000002:abnormalities*; D017809:Fatal Outcome; D006330:Heart Defects, Congenital / Q000150:complications* / Q000235:genetics / Q000601:surgery; D016027:Heart Transplantation; D018197:Hepatoblastoma / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D008297:Male; D009154:Mutation; D012868:Skin Abnormalities / Q000150:complications* / Q000235:genetics; D013577:Syndrome
chemical_list: D048369:MAP Kinase Kinase 1