Fanconi anemia, FANCC-related

What Is Fanconi Anemia, FANCC-Related?

Fanconi anemia is an inherited disorder in which the body cannot properly produce a protein that protects DNA from damage. This defective protein prevents the bone marrow from producing all types of blood cells. Without a sufficient number of red blood cells (anemia), the body does not receive enough oxygen, which can lead to abnormal bones and organs as well as developmental delay. A shortage of white blood cells (neutropenia) makes the body more susceptible to infection and cancer while a reduction in blood platelets (thrombocytopenia) makes it difficult for the blood to clot when an injury arises.

Fanconi anemia, FANCC-related is caused by mutations in the FANCC gene. There are at least 20 genes associated with Fanconi anemia.

In many cases of Fanconi anemia, the first symptoms appear in infancy as frequent nosebleeds, easy bruising, and physical abnormalities such as spotted skin or malformations of the thumbs, forearms, eyes, kidneys, gastrointestinal system, ears, or heart. Physical abnormalities can also include short stature and smaller-than-expected head size (microcephaly). However, 25 to 40% of individuals with the condition do not have physical abnormalities.

Children with the disease may also show signs of hearing loss or developmental delay and intellectual disability is observed in approximately 10% of cases. Diagnosis may first be made in childhood with abnormally low levels of red blood cells, white blood cells, or platelets. Although the bone marrow may appear normal at first, it deteriorates progressively and most children with the disease are diagnosed by age 12. Individuals with Fanconi anemia may have fertility issues and smaller-than-normal genitals.

Since Fanconi anemia prevents cells from repairing themselves when the DNA is damaged, individuals with the condition are at a higher-than-average risk of cancer. Occasionally, the initial signs of leukemia appear in childhood as the first symptom of the disease. Other cancers may also appear at an unusually early age, particularly tumors of the head and neck, esophagus, cervix, vulva, or liver. These cancers commonly develop in the patient's early twenties. Overall, about 30 to 40% of individuals with Fanconi anemia develop leukemia and/or other cancers, but the frequency of cancer rises with patient age.

How Common Is Fanconi Anemia, FANCC-Related?

The prevalence of Fanconi anemia is approximately 1 in 160,000 individuals worldwide and 1 in 130,000 individuals in the U.S. Fanconi anemia is most common in the Ashkenazi Jewish population, with a prevalence of 1 in 32,000 individuals. The FANCC gene accounts for about 14% of Fanconi anemia cases.

How Is Fanconi Anemia, FANCC-Related Treated?

There is currently no cure for Fanconi anemia. Treatment consists of monitoring for symptoms and treating them as they appear. About half of all individuals with the condition can improve their blood-cell counts with medication. Over a period of years, however, individuals often develop resistance to the medication. Treatment with medication may also decrease the effectiveness of a later bone marrow transplant.

Bone marrow transplantation can cure leukemia associated with Fanconi anemia. However, individuals with the condition are extremely sensitive to the chemotherapy and radiation treatments necessary to prepare for transplantation, so they may not be good candidates for this surgery. A bone-marrow transplant does not prevent solid tumors elsewhere in the body, and these must be treated with chemotherapy and radiation.

Individuals with Fanconi anemia must undergo regular blood-cell counts, bone marrow biopsies, liver scans, and gynecological, dental, and rectal exams to detect early-stage cancers so that they can be removed as soon as possible.

What Is the Prognosis for an Individual with Fanconi Anemia, FANCC-Related?

Most individuals with Fanconi anemia die before the age of 30. A bone marrow transplant can extend lifespan.