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 a normal level of 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, also called disruptive changes or alterations, in the ATM gene cause A-T.
How is A-T inherited?
Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 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 1 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 2 mutations and be affected with A-T. First-degree relatives, such as parents, siblings, 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 people interested in having a child when a prospective parent 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 specific known genetic mutations to reduce the likelihood that their children will inherit the condition. Eggs are removed and fertilized in a laboratory. When the embryos reach a certain size (approximately 8 cells), 1 cell is removed and is tested for the hereditary condition in question. The parent(s) can then choose to transfer embryo/s that do not have the mutation to the woman’s uterus. PGD has been in use for over 2 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 1 in 40,000 to 1 in 100,000 people. The chance that a person is a carrier of a single ATM gene mutation is about 1%, or 1 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 2 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 for an A-T gene mutation?
Carriers, meaning people with 1 ATM gene mutation, also have an increased risk of developing breast cancer. A carrier may also be called a heterozygote. Some studies have shown a 5 to 9 times higher lifetime risk for female breast cancer for carriers, but most studies have shown approximately 2 times the lifetime risk of developing female breast cancer compared to the general population. We do not yet know whether there is an increased risk of male breast cancer among ATM carriers. There are some data suggesting that ATM mutation carriers may also have an increased risk for colon and/or stomach cancers but this isn’t entirely clear. Clinical practice guidelines currently recommend that ATM mutation carriers have more screening for breast and colon cancer than the general population. There may also be an increased risk of pancreatic cancer among ATM mutation carriers.
Additional research is needed to clarify the risk of cancer and other conditions among ATM genetic 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 gene mutation carriers. Given the growing evidence of a moderate-to-high breast cancer risk among female ATM gene mutation carriers, the National Comprehensive Cancer Network (NCCN) now recommends that these women have breast cancer screening with yearly breast magnetic resonance imaging (MRI) in addition to a yearly mammogram and that all ATM gene mutation carriers have more frequent screenings with a colonoscopy (every 3-5 years, compared to every 10 years 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 health care team about appropriate screening tests.
Learn more about what to expect when having common tests, procedures, and scans.
Questions to ask the health care team
If you are concerned about your risk of cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking the following questions of your health care team:
What is my risk of developing cancer?
What is my risk of other types of cancer?
What can I do to reduce my risk of cancer?
What are my options for cancer screening?
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?
Will you refer me to a genetic counselor or other genetics specialist?
Should I consider genetic testing?
To find a genetic counselor in your area, ask your health care team or visit the following website: