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Fanconi anemia

Fanconi's anemia (FA) is a rare genetic disorder. Pathology: 1) hypoplastic pancytopenia of the bone marrow 2) cells from FA patients are particularly sensitive to cross-linking agents such as mitomycins, nitrogen mustard & psoralens 3) G2 prolongation is a feature of FA cells 4) other features of FA cells include oxygen sensitivity, G2 chromatid radiosensitivity & tumor necrosis factor (TNF) overproduction 5) interference with DNA topoisomerase activity may underlie the mechanism of oxygen-exacerbated G2 prolongation (active oxygen species induces a G2 delay in proliferating fibroblasts.) 6) FA is usually categorized with inherited cancer-prone conditions with defects in DNA repair; however, the relationship to DNA repair is inferential & the susceptibility of FA patients to malignancies is not as marked as other hereditary neoplastic syndromes 7) immune status of FA patients is not well documented; nhowever, defects in cell-mediated immunity & serum IgA have been reported 8) absence of Fanconi anemia complementation group complex (FA complex) Genetics: 1) autosomal recessive 2) caused by defect in one of the genes encoding subunits of the Fanconi anemia complementation group complex (FA complex), PHF9/FANCL, FANCA, FANCC, FANCE, FANCF, FANCG, FANCM 3) other implicated genes FANCI, BRCA2 Clinical manifestations: 1) short stature 2) dark pigmentation of the skin 3) skin hemorrhages 4) hypogonadism 5) hyper-reflexia 6) skeletal abnormalities esp. of the radius & thumb Laboratory: 1) complete blood count (CBC): progressive pancytopenia 2) chromosomal breakage in blood by diepoxybutane - diagnosis of FA includes finding of chromosomal breakage after incubation of the patient's cells with cross-linking agents such as diepoxybutane (DEB) or mitomycin C (MMC) [2] 4) preimplantation genetic diagnosis is available [4] Complications: - FA patients have a slightly increased risk of malignancies, in particular lymphocytic leukemia. Management: - allogenic bone marrow transplantation a) indications: 1] aplastic anemia 2] leukemia b) lower doses of cytotoxic drugs used c) FA patients are more susceptible to organ toxicity from chemotherapy

Related

Fanconi anemia complementation group complex (FA complex) Fanconi renotubular syndrome preimplantation genetic diagnosis (PGD) zinc finger & BTB domain-containing protein 32 (Fanconi anemia zinc finger protein, testis zinc finger protein, FANCC-interacting protein, ZBTB32, FAZF, TZFP)

Specific

Fanconi anemia complementation group A Fanconi anemia complementation group B Fanconi anemia complementation group C Fanconi anemia complementation group D (Estren-Dameshek variant of Fanconi anemia) Fanconi anemia complementation group J Fanconi anemia complementation group N

General

bone marrow disease chromosomal instability syndrome hereditary neoplastic syndrome; cancer susceptibility syndrome

References

  1. Ponz de Leon Recent results in cancer res. 136:322 1994
  2. Liu et al Blood 84:3995 1994
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  4. Journal Watch 21(14);117, 2001 Verinsky et al, JAMA 285:3120, 2001 Damewood, JAMA 285:3143, 2001
  5. Fanconi Anemia Mutation Database http://www.rockefeller.edu/fanconi/mutate/

Databases & Figures

OMIM correlations Human Disorders of DNA Repair