title: Fanconi anemia with biallelic FANCD1/BRCA2 mutations - Case report of a family with three affected children.
abstract: Fanconi anemia, complementation group D1 with bi-allelic FANCD1 (BRCA2) mutations, is a very rare genetic disorder characterized by early onset of childhood malignancies, including acute leukemia, brain cancer and nephroblastoma. Here, we present a case report of a family with 3 affected children in terms of treatment outcome, toxicity and characterization of the malignancies using comprehensive cytogenetic analysis. The first child was diagnosed with T-cell acute lymphoblastic leukemia when he was 11 months old. During chemotherapy, he suffered from repeated pancytopenia, sepsis and severe vincristine polyneuropathy, and 18 months after primary diagnosis, he succumbed to secondary acute monocytic leukemia. The second child was diagnosed with stage 2 triphasic nephroblastoma (Wilms tumor), when he was 3 years and 11 months old. During chemotherapy, he suffered from vincristine polyneuropathy. Currently, he is in complete remission, 29 months following the initial diagnosis. The third child was diagnosed with medulloblastoma with classical histology, when she was 4 years and 5 months old. After the first cycle of chemotherapy, she suffered from prolonged pancytopenia, sepsis and severe skin and mucosal toxicity. Six weeks after primary diagnosis, a first relapse in the posterior fossa was diagnosed, and at 7 and half months after primary diagnosis, a second relapse was diagnosed that led to the patient's death. Our case report underscores tumor heterogeneity, treatment toxicity and poor outcome in Fanconi anemia patients of complementation group D1.
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic. Electronic address: karel.svojgr@fnmotol.cz.
authors.forename: Karel
authors.initials: K
authors.lastname: Svojgr
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Sumerauer
authors.affiliation: Department of Biology and Medical Genetics, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Puchmajerova
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ales
authors.initials: A
authors.lastname: Vicha
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hrusak
authors.affiliation: Center of Oncocytogenetics, General Teaching Hospital, Prague, Czech Republic.
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalova
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Malis
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Smisek
authors.affiliation: Department of Radiology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kyncl
authors.affiliation: Department of Biology and Medical Genetics, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Drahuse
authors.initials: D
authors.lastname: Novotna
authors.affiliation: Department of Epidemiology and Cancer Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Machackova
authors.affiliation: Czech Gene Bank, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Jencik
authors.affiliation: Department of Pediatric Surgery, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Pycha
authors.affiliation: Department of Neurosurgery, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Vaculik
authors.affiliation: Department of Pathology and Molecular Medicine, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Kodet
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D024682:BRCA2 Protein / Q000235:genetics*; D002675:Child, Preschool; D005190:Family; D005199:Fanconi Anemia / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D024682:BRCA2 Protein
keywords: BRCA2; FANCD1; Fanconi anemia; Leukemia; Medulloblastoma; Wilms tumor