What is ataxia-telangiectasia?
Ataxia-telangiectasia (A-T) is a hereditary condition characterized by progressive neurologic problems that lead to difficulty walking and an increased risk of developing various types of cancer. Signs of A-T often develop in childhood. Children with A-T may begin staggering and appear unsteady (called 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 develop slurred speech and have difficulty with writing and other tasks. Red marks called telangiectasias are caused by dilated capillaries, meaning tiny blood vessels, and may 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 is passed from generation to generation in a family. The gene associated with A-T is ATM, meaning 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 with A-T. First-degree relatives, such as parents, brothers, sisters, and children of a person with A-T, have a 50% chance of inheriting the single gene mutation and becoming a carrier.
Options exist for couples interested in having a child when they know that one of them carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, one cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos that do not have the mutation. PGD has been in use for over two decades, and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.
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 people. The chance that a person is a carrier of a single ATM gene mutation is about 1%, or one in 100.
How is A-T diagnosed?
A-T is suspected whenever a child develops signs of ataxia, meaning unsteady walking. Testing of the ATM gene is available, and genetic mutations can be identified in about 90% of people with A-T. 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 3 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.
What are the estimated cancer risks associated with being a carrier or heterozygote for an A-T gene mutation?
Carriers, meaning people with one ATM gene mutation, also have an increased risk of developing breast cancer. Some studies have shown a 5 to 9 times higher lifetime risk for breast cancer for women who are carriers, while other studies have shown 2 times the lifetime risk of developing breast cancer compared to the general population. We do not yet know whether there is an increased risk of breast cancer among male ATM carriers. There are some data suggesting that male and female ATM mutation carriers may also have an increased risk for colon and/or stomach cancer but this isn’t entirely clear.
Additional research is needed to clarify the risk of cancer and other conditions among ATM mutation carriers. Studies also show that carriers may have an increased risk of heart disease.
As testing for hereditary cancer expands to include multiple-gene panels, the classical definition of syndromes such as A-T may change. Some people may have mutations in the ATM genes yet may not meet any of the criteria listed above for A-T. It is not known whether these people have the same risks of developing cancer.
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. People with A-T who frequently develop infections are encouraged to have their immune status checked regularly.
Cancer screening guidelines are evolving for ATM mutation carriers. Given the growing evidence of a moderate-to-high breast cancer risk among female ATM mutation carriers, the National Comprehensive Cancer Network (NCCN) now recommends that these women undergo breast cancer screening with yearly breast magnetic resonance imaging (MRI) in addition to a yearly mammogram. There are no specific guidelines yet for colorectal cancer screening among ATM mutation carriers, but some experts advise more frequent screenings with a colonoscopy every 3 to 5 years than for the general population.
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.
Learn more about what to expect when having common tests, procedures, and scans.
Questions to ask the doctor
If you are concerned about your risk of cancer, talk with your doctor. Consider asking the following questions of your doctor:
What is my risk of developing cancer?
What can I do to reduce my risk of cancer?
What are my options for cancer screening and prevention?
If you are concerned about your family history and think your family may have A-T, consider asking the following questions:
Does my family history increase my risk of developing cancer?
Could my family have A-T?
Should I consider genetic testing?
Should I meet with a genetic counselor?
A-T Children’s Project
National Ataxia Foundation
Facing Our Risk of Cancer Empowered (FORCE)
National Cancer Institute
American Cancer Society
To find a genetic counselor in your area, ask your doctor or visit these websites:
National Society of Genetic Counselors
National Cancer Institute: