Ataxia-Telangiectasia

Ataxia-telangiectasia (A-T) is a hereditary condition characterized by progressive neurologic problems that lead to difficulty walking. Signs of A-T often develop in childhood. Children with A-T may begin staggering and appear unsteady (ataxia) shortly after learning to walk. Most people with A-T will eventually need to use a wheelchair. People with A-T have normal intelligence, but over time, they will develop slurred speech and have difficulty with writing and other tasks. Red marks called telangiectasias are caused by dilated capillaries (tiny blood vessels) and appear on the skin and eyes as people get older. People with A-T also have a weakened immune system and are prone to infections. In addition, they appear to be particularly sensitive to ionizing radiation (such as x-rays) and have an increased risk of cancer.

What causes A-T?

A-T is a genetic condition. This means that the risk for A-T can be passed from generation to generation in a family. The gene associated with A-T is ATM (ataxia telangiectasia mutated). Mutations (changes) in the ATM gene cause A-T.

How is A-T inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. A-T follows an autosomal recessive inheritance pattern. In autosomal recessive inheritance, a mutation must be present in both copies of the gene in order for a person to be affected. This means that each parent must pass on a gene mutation for a child to be affected. A person who has only one copy of the gene mutation is called a carrier. When both parents are carriers of a recessive gene mutation, there is a 25% chance that a child will inherit two mutations and be affected.

How common is A-T?

A-T is rare. It is estimated that A-T affects one in 40,000 to one in 100,000 individuals. The chance that a person is a carrier of a single ATMgene mutation is about 1%, or one in 100.

How is A-T diagnosed?

A-T is suspected whenever a child develops signs of ataxia (unsteady walking). Testing of the ATM gene is available, and about 90% of mutations can be found. The following tests may be more helpful in determining if someone has A-T or another type of ataxia:

Immunoblotting (ATM protein testing). This is the best test to diagnose A-T. Nearly all individuals with A-T will have very low or no amounts of the protein made by the ATM gene.

Radiosensitivity assay. Since people with A-T have an increased sensitivity to radiation, removing some cells and treating the sample with radiation therapy can help make the diagnosis. It can take up to three months to get a result from this test.

ATM kinase activity. This test looks at the activity level of the protein made by the ATM gene. Little to no activity means that there is likely a mutation in the ATM gene.

What are the estimated cancer risks associated with A-T?

People with A-T also have about a 40% risk of developing cancer. The most common types of cancer seen in people with A-T are leukemia and lymphoma. These two types of cancers can appear in childhood and account for 85% of all cancers in people with A-T. As people with A-T live longer, there appears to be an increased risk of other cancer types, including breast cancer, ovarian cancer, stomach cancer,melanoma, and sarcoma.

Carriers (people with one ATM gene mutation) also seem to have an increased cancer risk. It is estimated that carriers have a 4% increase in cancer risk compared with the general population. Of particular concern is the potential breast cancer risk in women who carry an ATMgene mutation. Some studies have shown a large increase in breast cancer risk for women who are carriers, while other studies have shown no increased risk. Additional research is needed to clarify the cancer risk for ATM mutation carriers. Studies also show that carriers may have an increased risk of heart disease.

What are the screening options for A-T?

Children and adults with A-T should see their doctor regularly and be monitored for signs of cancer. Individuals with A-T who frequently develop infections are encouraged to have their immune status checked regularly.

There are no specific cancer screening or prevention recommendations for individuals with A-T or gene mutation carriers. However, women who are carriers are encouraged to talk with their doctor about breast cancer screening options.

Screening options may change over time as new technologies are developed and more is learned about A-T. It is important to talk with your doctor about appropriate screening tests.