Fanconi Anemia

At a glance

Fanconi anemia (FA) is the most frequently reported of the rare inherited bone marrow failure syndromes. It is a rare autosomal recessive inherited bone marrow failure syndrome with congenital and hematological abnormalities. Inherited anemia leading to bone marrow failure, myelogenous leukemia, and, in older patients, many cancers (head and neck, esophageal, gastrointestinal, vulvar, anal). It is recommended to use regional anesthesia when after confirming the absence of thrombocytopenia, in an attempt to limit the exposure to general anesthesia, particularly N₂O. The presence of microcephaly (possible difficult tracheal intubation), hypothyroidism, and elevated liver enzymes must be evaluated before general anesthesia.

Synonym

Fanconi Pancytopenia Type I Syndrome.

History

Genetically inherited anemia. Named after the Swiss pediatrician, Guido Fanconi.

Incidence

Rare, with carrier frequency of 1:300 in the general population (1:89 in the Ashkenazi Jewish population). Occurs equally in males and females and is found in all ethnic groups. The International Fanconi Anemia Registry (Rockefeller University, New York, NY) maintains case data on more than 3000 patients.

Genetic inheritance

Fanconi anemia (FA) comprises a group of monogenic autosomal recessive disorders resulting from mutations in one of eight Fanconi anemia genes (A, B, C, D1, D2, E, F, G). Although caused by rather simple mutations, the disorder shows a complex phenotype with many features, including developmental abnormalities, severe anemia, and/or eventually leukemia and various cancers. Many patients die during their mid-teen years. Mutations in FA-A and FA-C have been observed and account for 76% of affected patients worldwide.

Pathophysiology

Spontaneous chromosomal aberrations associated with hypocellular marrow, pancytopenia, and constitutional aplastic anemia.

Diagnosis

Usually diagnosed by age 6 years, after onset of hematologic abnormalities. It may be diagnosed as early as the neonatal period while investigated for other associated anomalies. Diepoxybutane, a DNA cross-linking agent, is a unique marker for Fanconi anemia cells. Currently, the definitive diagnostic test is a chromosome breakage test with a chemical, either diepoxybutane or mitomycin C, that cross-links DNA. Normal cells are able to correct most of the damage caused by these agents, whereas Fanconi anemia cells show marked chromosome breakage. These tests can be performed prenatally on cells from chorionic villi or from the amniotic fluid.

Clinical aspects

Pancytopenia, with mean survival of 5 years after diagnosis, low birth weight, skeletal anomalies (hips, spine, ribs), short stature, microcephaly, microphthalmia, microstomia, radial ray/thumb abnormalities, polydactyly, syndactyly, misplaced radial artery, renal abnormalities, cardiac defects, and developmental delay.

Precautions before anesthesia

Check a complete blood cell count (CBC) for anemia and thrombocytopenia. Check electrolytes in presence of renal defects. Complete physical evaluation must be obtained ...