FANCONI’S PANCYTOPENIA  

This is an autosomal recessive condition, with at least 8 subgroups (1).

60% of affected individuals show congenital malformations. The prognosis is poor, with 35% of patients dying at a mean age of 13 years due to frequent respiratory infections caused by the leukopenia (2).

Giampietro et al. (4) analyzed clinical data from 370 patients with Fanconi anemia and reported that only 220 individuals presented congenital anomalies. Although 60% of affected individuals showed congenital malformations, diagnosis before the onset of hematologic manifestations was made in only 28%. The prognosis of this genetically heterogeneous disorder is poor, with 35% of patients dying at a median age of 13 years due to frequent respiratory infections caused by leukopenia (2).

 

Diagnosis can be made by amniocentesis or cordocentesis and the subsequent induction of a high frequency of chromosomal breakage in lymphocytes and in cultured amniotic fluid cells by diepoxybutan and mitomycin C.

  1. Bone marrow failure (anemia, leukopenia, thrombocytopenia). Leukemia and the risk of malignant neoplasm is three to four times higher than that of the general population (5).
  2. Skeletal anomalies.
    • Radial club hand.
    • Absent thumbs.
    • Radial hypoplasia.
  3. Micrognathia, microcephaly and mental retardation
  4. Central nervous system:
    • Hydrocephalus.
    • Callosal agenesis.
    • Neural tube defects.
    • Single ventricle.
  5. Increased nuchal translucency (6).
  6. High frequency of chromosomal breakage.
  7. IUGR.
  8. Less common anomalies include:
    • Congenital dislocation of the hip.
    • Scoliosis.
    • Cardiac, pulmonary and gastrointestinal anomalies.
    • Splenic hypoplasia.

 

Hypoplastic radius                Normal ulna

Radial clubhand

 

 

Micrognathia / retrognathia

 

Agenesis of the corpus callosum

 

 

REFERENCES
      1. Joenje H, Oostra AB, Wijker M et.al. Evidence for at least 8 Fanconi anemia genes. Am J Hum Genet 1997;61:940-944.
      2. Butturini A, Gale RP, Verlander PC et.al. Hematologic abnormalities in Fanconis anemia: an International Fanconi Anemia Registry study. Blood 1994;84:1650-1655.
      3. Rosendorf J, Bernstein R. Fanconi’s anemia – chromosome breakage studies in homozygotes and heterozygotes. Cancer Genet Cytogenet 1988;33:175-183.
      4. Giampietro PF, Adler-Brecher B, Verlander PC, Pavlakis SG, Davis JG, Auerbach AD. The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. Pediatrics 1993; 91: 1116-1120
      5. Swift MR, Cohen J, Pinlcham R. Maximum likelihood method for estimating the disease predisposition of heterozygotes. Am J Hum Genet 1974;26:304-317.
      6. Tercanli S, Miny P, Siebert MS et.al. Fanconi anemia associated with increased nuchal translucency detected by first-trimester ultrasound. Ultrasound Obstet Gynecol 2001;17:160-162.