Fanconi anemia
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Introduction
Fanconi's anemia (FA) is a rare genetic disorder.
Pathology
- hypoplastic pancytopenia of the bone marrow
- cells from FA patients are particularly sensitive to cross-linking agents such as mitomycins, nitrogen mustard & psoralens
- G2 prolongation is a feature of FA cells
- other features of FA cells include oxygen sensitivity, G2 chromatid radiosensitivity & tumor necrosis factor (TNF) overproduction
- interference with DNA topoisomerase activity may underlie the mechanism of oxygen-exacerbated G2 prolongation (active oxygen species induces a G2 delay in proliferating fibroblasts.)
- 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
- immune status of FA patients is not well documented; nhowever, defects in cell-mediated immunity & serum IgA have been reported
- absence of Fanconi anemia complementation group complex (FA complex)
Genetics
- autosomal recessive
- 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
- other implicated genes FANCI, BRCA2
Clinical manifestations
- short stature
- dark pigmentation of the skin
- skin hemorrhages
- hypogonadism
- hyper-reflexia
- skeletal abnormalities esp. of the radius & thumb
Laboratory
- complete blood count (CBC): progressive pancytopenia
- 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]
- 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
- indications:
- lower doses of cytotoxic drugs used
- FA patients are more susceptible to organ toxicity from chemotherapy
More general terms
- hereditary neoplastic syndrome; cancer susceptibility syndrome
- chromosomal instability syndrome
- bone marrow disease
More specific terms
- 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
Additional terms
- 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)
References
- ↑ Ponz de Leon Recent results in cancer res. 136:322 1994
- ↑ 2.0 2.1 Liu et al Blood 84:3995 1994
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ 4.0 4.1 Journal Watch 21(14);117, 2001 Verinsky et al, JAMA 285:3120, 2001 Damewood, JAMA 285:3143, 2001
- ↑ Fanconi Anemia Mutation Database http://www.rockefeller.edu/fanconi/mutate/
Patient information
Fanconi anemia patient information