Fanconi Anemia

Fanconi anemia (FA) is a rare inherited disease characterized by multiple physical abnormalities, bone marrow failure, and a higher-than-normal risk of cancer. Researchers have shown that defects (mutations) in one of at least 15 different genes can cause FA. The proteins normally produced by these genes form a kind of cellular “machine” that helps detect and repair damaged DNA in blood stem cells and other cells in the body (a normal, daily occurrence). In FA, that DNA repair is slowed. Therefore, blood stem cells (in the bone marrow) accumulate damaged DNA and do not survive.

Fanconi anemia is usually discovered between birth and ages 10 to 15. However, there have been cases identified in adulthood. FA occurs equally in males and females. It has been identified in all ethnic groups. Researchers continue to clone and characterize the genes responsible for FA, which is bringing considerable progress in the diagnosis and understanding of this disease.

The most common symptoms of Fanconi anemia (FA) are:

• Extreme tiredness
• Frequent infections
• Easy bruising
• Nose or gum bleeding

These symptoms are due to low numbers or red blood cells, white blood cells or platelets. About 75% of children with Fanconi anemia have one or more of the following physical characteristics:

• Café au lait spots (light brown birth marks)
• Short stature
• Thumb and arm abnormalities (missing, misshapen, or extra thumbs or an incompletely developed/missing forearm bone)
• Low birth weight
• Small head or eyes
• Abnormalities of the kidneys, genitals, gastrointestinal tract, heart, and central nervous system.

Sometimes leukemia or myelodysplasia is the first sign of Fanconi anemia. Children with FA may only have a few of the clinical features or none at all.

Fanconi anemia is a genetic disease. It is 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 both of these affected genes are inherited, the child has FA. Carriers of the genetic defect (for example, the parents) do not have the disease.

In addition to a complete history and physical examination, other diagnostic tests are used to aid in the diagnosis of Fanconi anemia (FA). Initially, blood work is performed to evaluate the degree of anemia and examine other body systems. A chromosome breakage test called the DEB test is the standard, definitive test for FA at this time. However, researchers at Dana-Farber/Boston Children's Cancer and Blood Disorders Center are developing new, simpler and more rapid tests that may soon replace the DEB test. In addition, blood and bone marrow samples may be examined in order to identify the specific gene mutation present in the individual.

Specific treatment for Fanconi anemia and its complications will be determined by your child’s physician based on:

• Your child’s age, overall health, and medical history
• Extent of the disease
• Your child’s tolerance for specific medications, procedures, or therapies
• Expectations for the course of the disease
• Your opinion or preference

Treatment options for Fanconi anemia may include, but are not limited to, the following:

• Androgen therapy: Androgens are hormones that can improve the blood counts in approximately 50% of individuals with FA. They are taken daily, by mouth in liquid or pill form. Side effects of androgens include, but are not limited to: fluid retention and high blood pressure (hypertension), nausea, vomiting, acne, oily skin, enlarged penis/clitoris, hoarseness/voice deepening, hair growth or loss, behavioral changes, hot flashes, breast enlargement or tenderness, loss of menstruation, and liver toxicity.
• Growth factors: Growth factors such as G-CSF or GM-CSF stimulate the production of white blood cells. In some instances they may also improve red blood cell or platelet counts as well. They are given by injection.
• Stem cell transplant: At present, this is only cure for the blood defects in FA. Stem cell transplantation involves replacing of diseased blood-forming stem cells with another person’s healthy stem cells. Unfortunately it may not be an option for everyone. The success of a transplant depends on many factors, such as how close the match is between child and donor (matched siblings are best; if your child has a sibling, there is a 1 in 4 chance they will be a match) and the patient's age. The degree to which your child's bone marrow has failed also factors into the discussion whether to pursue a transplant.

In addition, stem cell transplants have many associated risks and therefore are not appropriate for many children with FA. The risks are compounded because FA makes individuals extremely sensitive to chemotherapy and radiation therapy, which are essential “pre” stem cell transplant therapies. The decision to proceed with stem cell transplant should be discussed with your child’s hematologist and a stem cell transplant team. Additional treatment alternatives are currently being studied.

Certain forms of cancer tend to develop in children with FA at a young age and may come back after treatment. These include:

• Leukemia
• Head and neck cancer (mouth, tongue, and throat)
• Gynecologic cancers (particularly labial, ano-genital, and cervical cancer)
• Gastrointestinal cancers (especially liver cancer)
• Brain tumors

The average lifespan for people with Fanconi anemia is 20 to 30 years. Children with a large number of birth defects are at higher risk of early onset severe aplastic anemia, while those with fewer abnormalities are more likely to develop leukemia or solid tumors as young adults. The most common cause of death is bone marrow failure, leukemia, or solid tumors.