Inherited anemia leading to bone marrow failure,
myelogenous leukemia, and, in older patients, many cancers (head and neck,
esophageal, gastrointestinal, vulvar, anal).
Type I Fanconi Pancytopenia.
Genetically inherited anemia. Named after the Swiss
pediatrician, Guido Fanconi.
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.
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 account for 76% of patients worldwide.
Spontaneous chromosomal aberrations associated
with hypocellular marrow, pancytopenia, and constitutional aplastic anemia.
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.
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.
Check a complete blood cell count (CBC) for anemia and
thrombocytopenia. Check electrolytes in presence of renal defects. Complete physical
evaluation must be obtained to eliminate the presence of cardiac defects.
Maintain oxygen carrying capacity with
red blood cell transfusion. Anticipate need for platelet transfusion. Avoid central
neuraxial anesthesia techniques in presence of coagulopathy. Direct laryngoscopy and tracheal intubation can be
difficult in the presence of macrostomia.
Prophylactic antibiotic must be considered
in case of cardiac defect.
Bloom Syndrome: Autosomal recessive inherited disorder
characterized by prenatal and postnatal growth retardation,
photosensitivity, telangiectasias, skin pigment anomalies, and increased
risk of malignancies most likely caused by chromosomal instability. Most
interchanges occur between homologous chromosomes, not between nonhomologous
chromosomes as in Fanconi anemia.
Blackfan-Diamond Syndrome: Congenital hypoplastic anemia
manifesting in the first year of life, with increased risk for leukemia.
High adenosine deaminase activity in the blood.
TAR Syndrome: Rare condition associated with ...