FANCONI ANEMIA



Fanconi Anemia: A review of this rare but important myelodysplasia

Mario Riportella

Eastern Virginia Medical School

Fanconi Anemia: A Review Of This Rare But Important Myelodysplasia

Fanconi Anemia

Fanconi Anemia: A review of this rare but important myelodysplasia Fanconi Anemia (FA) is a recessively inherited disorder characterized by pancytopenia, chromosomal instability and congenital anomalies. This disease predisposes patients to a variety of morbidity including aplastic anemia, pre malignancy, and premature mortality. While the incidence is considered rare presenting in approximately 1 per 100,000 live births, it is the most common inherited bone marrow failure syndrome. An estimated one quarter of children presenting with aplastic anemia are found to have Fanconi Anemia (Farzin, Davies, Smith, Filipovich, Hansen, Auerbach, and Harris, 2007). FA patients have a median survival of 24 years. In their lifetime, these patients are at a 500-1000 fold increased risk for developing squamous cell carcinomas, in particular those of the head and neck. Fanconi Anemia is found in near equal distribution amongst races with a male to female ratio of 1.2:1, typical of autosomal recessive disorders. (Kutler, Auerbach, Satagopan, et al 2003).

The condition was first described by the Swiss Pediatrician and ardent biochemistry researcher Dr. Guido Fanconi in 1927. His initial hypothesis of the disease process that would eventually bear his name focused on congenital anomalies and concomitant pancytopenia. In the 1960's, in vitro research focused on the cellular DNA instability of FA . Later in 2003, the 13 year Human Genome project coordinated between the U.S. Department of Energy and the National Institutes of Health was completed. This milestone in genetic science produced ripple affects across medicine disciplines and continues to promote greater understanding of genetic associations of disease manifestation. Specific to FA, a greater understanding of the genome helped researchers in FA discover the sensitivity to breakage of DNA cross linkers diepoxybutane (DEB) and mytomycin c (MMC) were identified as integral to the Fanconi Anemia disorder and made it possible to diagnose the disease in the approximately 25% of patients with aplastic anemia and/or pancytopenia but without obvious birth defects or congenital anomalies. More recent research in molecular diagnostics has uncovered subtle characteristics unique to FA patients and has led to the identification of the 13 genes known to be involved in the Fanconi Anemia -BRCA Pathway (Alter, Lipton, 2009).

Diagnosis

A workup for Fanconi Anemia includes a DNA fragility test of blood lymphocytes and flow cytometry evaluation, and should be considered in patients suspected of having FA. Particularly those with significant family history of anemia, physical abnormalities, or cancer. Siblings of patients diagnosed with FA should also be tested, as they have an equal pre-test probability and might serve as a potential blood/blood product donor if they indeed screen negative for FA.

Signs indicating the congenital anomaly syndrome referred to as VACTERL are of particular concern as these presentations have a high rate of association with the ultimate diagnosis of Fanconi Anemia and other chromosome disorders (Fanconi Anemia Research Fund, 2008). Included in the diagnosis of FA is the ...