What is FA?

What is Fanconi anemia?

Fanconi anemia (FA) is an inherited DNA-repair disease that may lead to bone marrow failure (aplastic anemia), leukemia, and/or solid tumors. It is primarily a recessive disorder: if both parents carry a defect (mutation) in the same FA gene, each of their children has a 25% chance of inheriting the defective gene from both parents. When this happens, the child will have FA.

Scientists have now discovered 23 FA or FA-like genes. FA occurs equally in males and females. It is found in all ethnic groups. Research has added years to the lives of people with FA. Decades ago, children rarely survived to adulthood. Research has resulted in better outcomes and longer lives for those with FA. There is now a growing population of adults living with FA. In late 2017, for the first time ever, there were more adults living with Fanconi anemia than children (according to FARF’s registry). This reflects an emerging population of adults that was not present even just a decade ago. This growth in the adult population could be attributed to the dramatic increase in survival following stem cell transplants over the last 20 years. As a result, more children are reaching adulthood.

According to FARF’s internal database of individuals with FA:

  • More than half of the FA population is age 18 or over
  • Approximately 60 newly-diagnosed individuals register with FARF each year
  • Nearly 1,000 people living with FA are connected to FARF

FA can affect all systems of the body. The types and severity of symptoms can differ widely from person to person. Many people with FA eventually develop acute myeloid leukemia (AML). FA patients are extremely likely to develop a variety of cancers and at a much earlier age than patients in the general population. Patients who have had a successful bone marrow transplant and are therefore cured of the blood problem associated with FA still must have regular examinations to watch for signs of cancer.


The FA Diagnosis

Fanconi anemia usually reveals itself before children are 12 years old, but in some cases, no symptoms are present until adulthood. Fanconi anemia patients are usually smaller than average. They may feel extreme fatigue and have frequent infections. Nosebleeds or easy bruising may be a first sign of the disease. Blood tests may reveal a low white cell, red cell or platelet count or other abnormalities. Sometimes myelodysplasia, AML, or squamous cell carcinoma in a young adult is the first sign of FA.

Physical Defects

FA is sometimes evident at birth through a variety of physical defects. These may include any of the following:

  • Hand and arm anomalies: misshapen, missing or extra thumbs or an incompletely developed or missing radius (one of the arm bones).
  • Skeletal anomalies of the hips, spine, or ribs.
  • Kidney problems, including missing or horseshoe kidney.
  • Skin discoloration (café-au-lait spots); portions of the body may have a suntanned look.
  • Small head or eyes.
  • Mental retardation or learning disabilities.
  • Low birth weight.
  • Gastrointestinal difficulties.
  • Small reproductive organs in males.
  • Defects in tissues separating chambers of the heart.

Testing for FA

The definitive test for FA is a chromosome breakage test: some of the patient’s blood cells are treated, in a test tube, with a chemical that crosslinks DNA. Normal cells are able to correct most of the damage and are not severely affected, whereas FA cells show marked chromosome breakage. The two chemicals commonly used for this test are DEB (diepoxybutane) and MMC (mitomycin C). These tests can be performed prenatally on cells from chorionic villi or from the amniotic fluid.

Many cases of FA are not diagnosed at all or not diagnosed in a timely manner. FA should be suspected and tested for in any infant born with the thumb and arm abnormalities described previously. Anyone developing aplastic anemia at any age should be tested for FA, even if no other defects are present. Many people with FA show no other abnormalities.

It is absolutely essential to test for FA before contemplating bone marrow transplantation for aplastic anemia. The regimen used to prepare patients for transplant is very different for FA patients, as FA patients tolerate radiation and chemotherapy very poorly.

Carrier Frequency

While the total number of people with FA is not documented worldwide, scientists estimate that the carrier frequency (carriers are people carrying a defect in an FA gene, whose matching FA gene is normal) for FA in the U.S. is 1 in 181. The incidence rate, or the likelihood of a child being born with FA, is about 1 in 131,000 in the U.S., with approximately 31 babies born with FA each year in this country.**

**Rosenberg, P. S., Tamary, H. and Alter, B. P. (2011), How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel. American Journal of Medical Genetics Part A, 155: 1877–1883. doi: 10.1002/ajmg.a.34087