Fanconi anemia: Year of the Zebra 2025

Fanconi anemia, or FA for short, is a rare genetic disorder that affects the body's ability to repair damaged DNA.

For cells to function properly, DNA needs to remain intact in order to pass on or express genetic information. Unfortunately, DNA damage is common, and it happens all the time due to toxic substances from cell metabolism and environmental factors, like cigarette smoke or radiation. Luckily, cells have specific DNA repair mechanisms that try to fix this damage and prevent too many DNA mutations from occurring.

In FA, a network of proteins responsible for DNA repair and integrity don’t work properly, allowing damage to pile up. Affected cells either die or accumulate too many DNA mutations, increasing the risk of cancer, especially leukemia and tumors.

Because FA affects cells during early development, most individuals have congenital birth defects, including a short stature, missing thumbs, kidney problems, and skin changes like café au lait spots. In cases where these signs aren’t apparent, diagnosis tends to be delayed until the development of bone marrow failure, which is one of the most common features of FA.

Bone marrow failure usually occurs in childhood or early adulthood, when the bone marrow stops producing enough blood cells, leading to low levels of red blood cells, white blood cells, and platelets. This results in severe complications, including an increased risk of life-threatening anemia, infections, and bleeding problems.

Individuals with FA also have a high risk of developing myelodysplastic syndrome, a bone marrow disorder that can progress to acute leukemia. They also have a higher risk of developing tumors at an earlier age than the general population, especially in the head, neck, and pelvic areas.

Diagnosis of Fanconi anemia is suspected in individuals with unexplained bone marrow failure and associated birth defects. Diagnosis can be confirmed with a chromosome breakage test, a blood test that assesses chromosomal instability. If the chromosome breakage test is positive, genetic testing may be done to identify the mutated FA gene and determine if family members carry the same mutation. Additional tests may include a bone marrow biopsy and cancer screening tests for early tumor detection.