Clinical suspicion of Fanconi's anemia

When Fanconi described a family with three children with birth defects and aplastic anemia (AA), he made the first clinical observation of what is now clearly a hematological syndrome (Fanconi, 1927). After a few more such families were recognized by others, Fanconi's name was assigned to this phenotype, which is now called Fanconi's anemia (abbreviated FA). In many ways, we have come a long way since then, with the knowledge that there may be at least eight genes responsible for this autosomal recessive condition (Joenje et al., 1997), the cloning of three and mapping of a fourth gene (de Winter et al., 1998; Lo Ten Foe et al., 1996; Strathdee et al., 1992a,b, The Fanconi Anaemia/Breast Cancer Consortium, 1996; Whitney et al., 1995), and substantial insights into the evolution and treatment of many of the complications of this disorder (see Alter and Young, 1998; Young and Alter, 1994 for recent reviews). However, we still do not always know who to suspect of this condition, precisely how to definitively diagnose or exclude it, how to predict the course of a specific patient, and how to cure or even treat many patients. Given many caveats with regard to biased and possibly incorrect ascertainment, more than 1000 cases of FA have been reported in the literature, with a male:female ratio of 1.3:1. The average age at diagnosis is 7.8 years for males, and 8.8 years for females, with a range from birth to adults.