Fanconi Anemia (FA): A Comprehensive Overview of Genetics, Symptoms, and Disease Progression

Fanconi anemia (FA) is an autosomal recessive disease caused by a biallelic mutation which mainly occurs in proteins involved in the cell cycle, from DNA synthesis to replication and regeneration. The carrier frequency of disease is 1:300 of live births in the general population. The male-to-female ratio is 1.9:1. The chromosomal breakage test was considered the gold standard for the diagnosis of the disease but for the confirmation genetic analysis is mandatory because other syndrome can mimic with the FA. The disease is mainly characterized by physical abnormalities such as microcephaly, short stature with skeletal anomalies of both limbs, defective genitourinary system and abnormalities of the eyes. Bone marrow dysfunction is usually observed from the first decade of life which initially starts as thrombocytopenia or pancytopenia and later progresses to bone marrow failure. As patients enter their teenage or adulthood, they encounter a high risk of myelodysplastic syndrome and acute myeloid leukemia. To date, 22 genes are associated with FA. The genetic foundation of FA highlights several FANC genes, particularly FANCA, FANCC, FANCG, and FANCD2, which are the most commonly mutated. There are distinct patterns of somatic chromosomal abnormalities seen in FA patients, especially unbalanced chromosomal translocations that result in partial duplication or deletions. The mechanisms underlying the hematopoietic defects and clonal evolution in FA are still largely unknown; however, understanding these processes is essential for enhancing patient management and treatment.