> Fanconi Anemia

• Alternative Names
• Symptoms & Characteristics
• Treatment
• How Common Is It?
• Genetics & Inheritance
• Genetic Testing
• Support & More Information

Alternative Names

Fanconi pancytopenia; fanconi's anemia

Symptoms & Characteristics

Fanconi anemia (FA) is a genetic condition characterized by physical abnormalities, bone marrow failure and an increased risk to develop cancer.

Physical abnormalities are present in about 60%-75% of affected people and can include:

• short stature

• abnormal skin pigmentation

• forearm and thumb malformations

• skeletal abnormalities

• eye and ear malformations

• kidneys and urinary tract malformations

• heart defects

• gastrointestinal malformations

• brain and spinal cord (the central nervous system) defects

• hearing loss

• underdeveloped reproductive organs

• developmental delay

By age 40 to 48 years, the majority of affected people experience bone marrow failure. Affected people also have an increased risk to develop leukemia and other types of cancer (particularly tumors of the head and neck, skin, gastrointestinal tract, and genital tract).

Treatment

There is no cure for fanconi anemia. Early diagnosis, routine surveillance and treatment may help to manage some of the symptoms.

How Common Is It?

About 1 in 100,000 live births are affected with fanconi anemia

Genetics & Inheritance

Fanconi anemia is caused by mutations in one of several different genes. Fanconi anemia is categorized into 13 groups called complementation groups each of which has an associated gene.

Various mutations have been documented in the genes that cause fanconi anemia.

• One specific mutation in the FANCC gene that causes FA group C is more common in people of Ashkenazi (eastern and central European) ancestry.

• Mutations in the BRCA2 gene (also known as FANCD1) are associated with hereditary breast and ovarian cancer.

• Mutations in the BRIP1 (also known as FANCJ) and PALB2 (also known as FANCN) genes have also been implicated in breast cancer predisposition.

We all have two copies of most genes - one from each parent. In all FA complementation groups (with the exception of FA group B), it is necessary to have two mutations, one in each gene copy, to be affected. This is called autosomal recessive inheritance.

• Both parents of an affected person are always both obligate carriers (each have only one mutation). Two carriers have a 25% chance with each pregnancy to have an affected child, but do not have symptoms themselves.

• Without a family history, the chance to be a carrier is determined by a person's ethnic background. For example, about 1 in 90 people of Ashkenazi Jewish ancestry are carriers of fanconi anemia. People of black South African and Spanish Gypsy ancestry are also at increased risk to be carriers.

FA group B has X-linked recessive inheritance. X-linked means the mutated gene is located on the X chromosome. Females have two X chromosomes, while males have one X chromosome and one Y chromosome. In a male, an X-linked recessive condition is expressed in everyone with a mutation in a single gene; as men do not have a second X chromosome and therefore, a second gene to compensate. In a female, an X-linked recessive condition is expressed in everyone with two mutations, one in each gene copy. Females with only one mutation are considered carriers, and typically do not have any symptoms.

There are other genetic conditions that have symptoms which overlap with fanconi anemia. A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.

Genetic Testing

Clinical genetic testing for fanconi anemia can be broken down into two categories: diagnostic testing and carrier testing.

• Diagnostic testing may be used to confirm or rule out a diagnosis in a person suspected to have the disorder. Alternatively, special testing called chromosomal breakage studies may also be used confirm or rule out a diagnosis. Chromosomal breakage studies test for increased chromosomal breakage or rearrangements when cells are exposed to a chemical agent. Chromosome breakage studies cannot identify DNA mutations.

• Carrier testing is typically offered after a clinical diagnosis and/or mutations have already been identified in an affected family member(s). Carrier testing is also available for people of high risk ethnic groups.

Carrier testing for the Ashkenazi-specific mutation that causes fanconi anemia group C is available online (over the internet). This testing is available individually or as part of an Ashkenazi Jewish panel. Go to the Tests tab to link to the best providers, compare providers and read provider reviews.

Diagnostic testing and carrier testing for fanconi anemia groups A, B, C, E, F, G, and I may be available through an in person genetic consultation for people who are considered at risk. Genetic testing for fanconi anemia groups D1, D2, J, L, M, and N is currently available on a research basis only. Use our find a genetic professional directory to locate a trained genetic professional in your area.

• A medical geneticist can also be found at the American College of Medical Genetics website.

• A genetic counselor can also be found at the National Society of Genetic Counselors website.

Support & More Information

More information can be found at:

• GENEReviews

Support can be found at:

• Fanconi Anemia Research Fund, Inc (FARF)