Fanconi anemia and cancer
Fanconi anemia is a rare inherited disorder that primarily affects the bone marrow, leading to reduced production of blood cells. This condition can significantly predispose individuals to various cancers, including acute myelocytic leukemia and squamous cell carcinoma, often appearing earlier in life than would typically be expected. The disease is caused by mutations in specific genes, with approximately 80 to 90 percent of cases linked to mutations in the FANCA, FANCC, or FANCG genes. Symptoms generally emerge between the ages of three and twelve and can include fatigue, increased susceptibility to infections, and physical abnormalities like stunted growth or malformations of the hands and spine.
Those affected by Fanconi anemia are at a heightened risk for developing various cancers, particularly leukemia and reproductive tract cancers in women. While there is no cure for the condition, treatment options such as bone marrow transplants and hormone therapies can help manage symptoms and improve blood cell counts. Despite the serious nature of the disease, advancements in medical care are improving life expectancy for individuals with Fanconi anemia, which averages around 22 years. Understanding this condition is crucial for those at risk and their families, as early diagnosis and intervention can greatly influence outcomes.
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Fanconi anemia and cancer
ALSO KNOWN AS: Fanconi’s anemia, FA, Fanconi hypoplastic anemia, Fanconi pancytopenia, Fanconi panmyelopathy
RELATED CONDITIONS: Leukemia, liver tumors, brain tumors, and cancers of the head, neck, esophagus, and female reproductive system
DEFINITION: Fanconi anemia is a rare inherited disease that affects bone marrow, resulting in reduced blood cell production. It is not the same as Fanconi syndrome, which is a rare kidney disorder.
Around 90 percent of children born with Fanconi anemia have bone marrow abnormalities. Bone marrow is the central part of the bones in which blood cells are produced. Red blood cells transport oxygen to the cells, white blood cells protect the body against infection, and platelets cause wounds to clot. Damage to the bone marrow decreases the production of all these types of blood cells.
Having this condition predisposes people to develop several kinds of cancers, including acute myelocytic leukemia (AML) and squamous cell carcinoma. These cancers will arise in a person with Fanconi anemia at a much earlier age than the cancers would normally occur.
Risk factors: Fanconi anemia is a recessive inherited disease, meaning both parents must have the disease genes for their children to develop it. Each child who has two parents with the disease genes will have a 25 percent chance of developing the condition.
Etiology and the disease process: Fanconi anemia is an inherited disease that stems from changes, called mutations, in genes. Genes hold the instructions for cells to make different proteins, which carry out various bodily functions. In people with Fanconi anemia, defective genes prevent the production of proteins needed for cells to work normally. Between 80 and 90 percent of Fanconi anemia cases arise due to mutations in the FANCA, FANCC, or FANCG genes. Fanconi anemia type D1 (FA-D1) occurs when two flawed copies of the BRCA2 gene exist in each cell.
Incidence: Healthcare professionals estimate that 1 in 90 people carry the genetic defect responsible for the condition. The incidence of Fanconi anemia is 1 in 160,000 people worldwide. The symptoms of Fanconi anemia most often emerge between the ages of three and twelve, although symptoms can remain dormant until later in life. The disease occurs equally among genders and races. However, there is a higher risk among people of Ashkenazi Jewish descent, Spain's Roma population, and Black South Africans. Between 18 and 20 percent of people with Fanconi anemia develop leukemia. Between 10 and 30 percent of individuals with the condition develop these cancers, most at a younger age than the general population.
Symptoms: The disease results in fewer white blood cells, making a person more susceptible to infections. A lower red blood cell count leads to fatigue, and platelet reduction can interfere with normal blood clotting. The first signs of the disease are often nosebleeds or bruising. People who have Fanconi anemia may have stunted growth; misshapen, missing, or extra thumbs; abnormal arm, hip, spine, or rib bones; a small head or eyes; kidney problems; an abnormal stomach, esophagus, or intestinal tract; intellectual disabilities; and learning disabilities. Patches of unevenly colored skin (café-au-lait spots) are also common. Men may have smaller than normal genitals. People with Fanconi anemia are more likely to develop leukemia and cancers of the head, neck, and esophagus. Women with the disease are at greater risk for reproductive tract cancers.
Screening and diagnosis: The primary test for Fanconi anemia is a chromosome breakage test, which mixes the patient’s white blood cells with special chemicals to see whether the chromosomes break more easily than they should.
Doctors can also diagnose the disease by removing a sample of bone marrow with a needle through a procedure known as bone marrow aspiration and examining that sample under a microscope to look for signs of low blood cell production. Another method is a bone marrow biopsy, in which a small needle is inserted into the bone to remove a piece of bone marrow for testing. Patients often have a complete blood count to look for low numbers of white blood cells, red blood cells, and platelets. Other screening methods include developmental tests and a kidney ultrasound. If there is a family history of Fanconi anemia, the condition can be diagnosed before a child is born using amniocentesis and chorionic villus sampling (CVS).
Treatment and therapy: A bone marrow transplant can treat blood cell problems, although it cannot reduce the risk of developing cancer or other problems (such as bone malformations) associated with Fanconi anemia. The bone marrow transplant is most likely to be successful if taken from a matched sibling.
Patients may take artificial versions of male hormones called androgens, which improve red blood cell counts and may also help improve white blood cell counts in certain patients. Hemopoietic growth factors, such as erythropoietin, can also increase blood counts, as can having a blood transfusion. Research on gene therapy treatment to correct genetic mutations to benefit Fanconi anemia patients is ongoing.
Prognosis, prevention, and outcomes: Because this is an inherited disorder, there is no way to prevent it, although it is possible to screen a fetus for the disease while in the womb. The average life expectancy for someone with Fanconi anemia is age twenty-two, although survival can vary between people. Modern technology and improved bone marrow transplantation outcomes are prolonging the life span of many individuals with this disease.
Bibliography
Bhandari, Jenish. "Fanconi Anemia." National Library of Medicine, 19 June 2024, www.ncbi.nlm.nih.gov/books/NBK559133. Accessed 20 July 2024.
"BRCA2 Gene." MedlinePlus, medlineplus.gov/genetics/gene/brca2. Accessed 20 July 2024.
Chen, Harold. Atlas of Genetic Diagnosis and Counseling. 4th ed. Springer, 2020.
"Fanconi's Anemia." MedlinePlus, medlineplus.gov/genetics/condition/fanconi-anemia. Accessed 20 July 2024.
Maclellan, Alec. Fanconi Anemia: Clinical, Cytogenic, and Experimental Aspects. Springer, 2012.
Mehta, Parinda A., and Christen Eben. "Fanconi Anemia." National Library of Medicine, 3 June 2023, www.ncbi.nlm.nih.gov/books/NBK1401. Accessed 20 July 2024.
Niraj, Joshi, et al. "The Fanconi Anemia Pathway in Cancer." Annual Review of Cancer Biology, vol. 3, no. 1, 2019, pp. 457-478. doi.org/10.1146/annurev-cancerbio-030617-050422.
Schindler, D., and H. Hoehn. Fanconi Anemia: A Paradigmatic Disease for the Understanding of Cancer and Aging. Karger, 2007.
Shamin, Ahmad, and Sandra H. Kirk, eds. Molecular Mechanisms of Fanconi Anemia. Scholars Portal, 2019.