Fanconi anemia is a clinically and genetically heterogeneous group of diseases that have the following features in common: a pre- and postnatal growth disorder; malformations of the heart, kidneys and skeleton, in particular radial and thumb malformations; pigmentation abnormalities; characteristic facial features and microcephaly of variable severity. Early bone marrow failure with an increased risk of leukemia and solid tumors, is characteristic. This is ultimately caused by a DNA repair defect, which causes increased sensitivity, especially to DNA crosslinking agents, and leads to genomic instability. Accordingly, there is increased chromosomal fragility with mitomycin C or diepoxybutane. More than 20 subtypes with pathogenic genes have been described, whereby more than half of the diseases are due to pathogenic variants in FANCA. Inheritance is mostly autosomal recessive, rarely autosomal dominant (FANCR – RAD51) or X-linked recessive (FANCB – FANCB). There are no genotype-phenotype correlations.
Regular (annual) screening examinations (bone marrow, interdisciplinary examinations to exclude solid tumors) are recommended for monitoring. Treatment involves the use of oral androgens to increase the number of red blood cells and platelets as well as G-CSF to increase the number of neutrophils. Stem cell transplantation can correct bone marrow deficiency, but not the increased risk of solid tumors.
Fiesco-Roa et al. 2019, Blood Rev 37:100589 / Nalepa et Clapp 2018, Nat Rev Cancer 18:168 / Nepal et al. 2017, Trends Cancer 3:840 / Ebens et al. 2017, Expert Rev Hematol 10:81 / Mamrak et al. 2017, Blood Rev 31:93 / Cheung et Taniguchi 2017, Int J Hematol 106:335 / Esteban-Jurado et al. 2016, Eur J Hum Genet 24:1501 / Alter 2014, Best Pract Res Clin Haematol 27:214