Rare autosomal recessive disease with progressive bone marrow failure, development abnormalities, increased risk of myelodysplasia, malignancies and especially acute leukemia.
The genetic disorder that is most commonly associated with aplastic anemia, a DNA repair defect that results from mutation in one of at least 15 known genes.
The second most common genetic disorder of bone marrow failure is this keratosis congenita due to a mutation in genes involved in telomere repair or protection.
Prevalence 1.5 per million.
There are 15 genes associated with FA.
The inheritance pattern of the 13 Fanconi associated anemia genes are autosomal recessive for subtypes of the disorder, except X-linked recessive disease (Wang W).
One of the genes associated with FA is the BRCA2 gene.
Genes associated with FA help to recognize and repair of damaged DNA, and they are inactivated by FA.
Usually present by end of first decade of life with a median age of 8 years.
Approximately 75% of patients have congenital anomalies including radial, hip, vertebral and rib abnormalities, short stature, developmental abnormalities, hydrocephalus, deafness, gastrointestinal atresia and cardiac abnormalities.
One third of patients have no congenital abnormalities.
A number of studies indicate that hematopoietic progenitor cell populations are apoptotic reflected by hypersensitivity of these cells to cytokines tumor necrosis factor and interferon gamma.
Cells exhibit chromosomal instability and hypersensitivity to DNA interstrand cross linking agents, like cisplatin and bifunctional alkylating agents.
Cultured cells more susceptible to chromosome breakage and is the definitive test for the diagnosis of FA (Auerbach AD).