Ataxia-Telangiectasia

Ataxia-telangiectasia (A-T) is a rare genetic condition that affects the nervous system, immune system, and other body systems.

Children with this condition have trouble coordinating their movements, which is called ataxia. They also have small clusters of enlarged blood vessels called telangiectasias. These occur in the eyes and on the surface of the skin. People with this condition are at higher risk for developing certain types of blood cancers and immune system cancers.

Ataxia often begins before age 5 and progresses over time. Most children with A-T will eventually find it hard to walk and have problems with balance and hand coordination. They may have other nervous system problems as well, including:

• Slurred speech
• Trouble moving eyes from side to side
• Involuntary jerking movements
• Muscle twitches
• Issues with nerve function, called neuropathy

Cancer risk with ataxia-telangiectasia

People with A-T have about a 40% chance of developing cancer. Of those who develop cancer, most will develop leukemia (blood cell cancer) or lymphoma (immune cell cancer). Other types of cancer that may develop include:

• Ovarian cancer
• Breast cancer
• Thyroid cancer
• Parotid (salivary) gland tumors
• Gastric (stomach) cancer
• Melanoma (skin cancer)
• Leiomyomas (smooth muscle tumors)

Other health problems with ataxia-telangiectasia

People with A-T may have other medical problems. Not all people with A-T will have all the problems listed here. These vary from person to person.

• Weak immune system and frequent infections
• Sensitive to ionizing radiation, such as the radiation used for CT scans and medical x-rays
• Premature aging and graying of the hair
• Abnormal endocrine (hormone) system, including type 2 diabetes, short height, and delayed puberty
• Mild learning problems or mild intellectual disability
• Smaller-than-normal cerebellum (a part of the brain), which can be seen on an MRI exam after about ate 7 or 8

How severe the signs and symptoms of A-T are may vary between families. But people with A-T who are in the same family often have a similar disease.

Ataxia-telangiectasia cause

A-T is caused by changes in a gene known as ATM. Genes carry information telling cells in the body how to function. The ATM gene helps cells repair damaged genetic material (DNA). When genes are changed and do not work as they should, the changes are called mutations.

How ataxia-telangiectasia is inherited

Cells from people with A-T carry 2 ATM gene mutations. One mutation was inherited from the mother, and the other mutation was inherited from the father.

When both copies of the ATM gene have mutations, cells cannot repair damage to their DNA as well as someone with 2 working copies of the ATM gene. The cells become unstable and sometimes die or grow to form a tumor. That is why people with A-T are at higher risk of developing some kinds of cancer.

People with only 1 ATM mutation do not have A-T and do not show symptoms of the condition. These people are called carriers. Adults with 1 ATM mutation have slightly higher risks than the general population of developing female breast, ovary, prostate, and pancreas cancers. There are national cancer screening guidelines for adults with 1 ATM mutation.

The parents of a child with A-T have a 25% (1 in 4) chance of having another child with A-T. They have a 50% (1 in 2) chance of having another child who carries just 1 ATM mutation. That child would be a carrier. Carriers do not have A-T but can pass the ATM mutation to their own children.

There is a 25% (1 in 4) chance of having another child with no ATM mutations. That child would not have A-T and would not be a carrier. Children with no ATM mutations would pass on only normal copies of the ATM gene to their own children.

A person with A-T has different risks of having a child with A-T. A person with A-T will pass 1 ATM mutation to each of their children. A person with A-T’s chance of having a child with A-T depends on whether their partner also carries an ATM mutation. If the partner carries an ATM mutation, the chance of having a child with the condition is 50% (1 in 2). The chance of having a child who carries just 1 ATM mutation is 50% (1 in 2). If the partner does not carry an ATM mutation, no children will have A-T. But all the children will be carriers.

Ataxia-telangiectasia diagnosis

A doctor may suspect A-T based on signs and symptoms of the condition. 

Lab tests

Several lab tests can be used to support a diagnosis of ataxia-telangiectasia:

• Special tests can measure the amount of ATM protein in cells. The ATM gene makes a protein that is also called ATM. People with A-T usually have ATM protein levels in their cells that are much lower than normal.
• Blood tests measure the level of a protein called alpha-fetoprotein. More than 95% of people with A-T have high levels of alpha-fetoprotein. These levels are very low in most people without A-T.
• Radiosensitivity test can measure how well a cell can repair damaged DNA. Cells that contain working ATM protein should be able to repair themselves after being exposed to radiation. The cells from people with A-T do not typically survive after exposure to radiation because they do not repair DNA as well.
• Chromosome analysis can see how chromosomes reattach after breaking. Chromosomes are the part of the cell that contains the genetic material (DNA). This test can show when chromosomes break and the pieces reattach at the wrong place to other chromosomes.

Health history

A health care provider may suspect A-T after looking at a person’s medical or family history and after the lab tests listed above. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members.

If A-T is suspected in a child or other family members, the doctor or genetic counselor will likely suggest genetic testing of the ATM gene.

Learn more about types of genetic tests.

Genetic testing for ataxia-telangiectasia 

A blood sample is sent to a genetic testing lab. The lab runs genetic tests that looks for changes in the ATM gene. If your child has an ATM mutation, the genetic counselor will work with your family to:

• Find out if other family members should consider testing for an ATM mutation 

• Help your family understand the increased cancer risk from A-T

• Give you information to help with your decisions about prenatal genetic testing

Genetic testing before or during pregnancy

Parents may choose to do prenatal testing to find out if a pregnancy is affected with a known ATM mutation. Testing may take place either before pregnancy occurs or during pregnancy.

You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT offers a way to test embryos for known ATM mutations before placing them into the uterus.

Testing during pregnancy can help providers see if a pregnancy is affected with known ATM mutations. A doctor gathers cells from the pregnancy in 1 of 2 ways:

• Chorionic villus sampling (CVS) is done during the first trimester (first 3 months).
• Amniocentesis is done during the second trimester or later (last 6 months).

After tissue collection, the lab tests for known ATM mutations identified in the family.

Both tests carry minor risks. Discuss risks with an experienced health care provider or prenatal genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

Sometimes, children or adults with A-T feel sad, anxious, or angry after getting their test results. Parents may feel guilty if they pass the ATM gene mutation to 1 or more of their children. People with an ATM gene mutation may also have trouble getting disability or life insurance.

Read more about genetic discrimination.

Monitoring and follow-up care for ataxia-telangiectasia 

People with A-T should be monitored and have follow-up with a doctor who knows the condition well. Children with A-T need regular screenings to detect cancer as early as possible. The goal of screening is to find and treat cancer early for the best outcome. Recommended screenings may change over time as doctors learn more about A-T.

At this time, there are no guidelines for cancer screening in children with A-T. The following are recommended:

• Yearly lab tests, including complete blood count, complete metabolic panel, and lactate dehydrogenase. The tests screen for lymphoma and leukemia.
• Yearly physical exams by a doctor who knows this condition well, giving special attention to any signs of leukemia or lymphoma, such as weight loss, bruising, pain, or swelling.
• Yearly check-ups with the child’s regular pediatrician.

People with A-T are more sensitive to the effects of radiation. It may increase their risk of developing cancer. People with A-T should avoid medical tests that use radiation, such as CT scans, x-rays, and mammograms. A health care provider may decide that these tests are needed if the benefit outweighs the risk. Also, people with A-T require special care when anesthesia is needed.

Because of the other medical concerns related to A-T, the following specialists are an important part of the health care team:

• Neurology
• Immunology
• Supportive therapy, such as physical, occupational, and speech therapies

Living with ataxia-telangiectasia

People of any age with A-T have a higher risk of cancer. It is important that they find a health care team for follow-up and adopt healthy habits throughout life. It is important to continue to have regular physical checkups and screenings. That way, any cancer can be found early at the most treatable stage.

Problems to watch for

Those with A-T should closely watch for signs or symptoms that could signal cancer, such as:

• Unexplained weight loss
• Loss of appetite
• Easy bruising
• Blood in the stool or changes in bowel habits
• Aches, pains, lumps or swelling for no clear reason
• Headaches or changes in vision or nerve function that do not go away

Seek medical help if anything unusual appears.

Maintain a healthy lifestyle 

Habits that will help you maintain a healthy lifestyle include:

• Eat a healthful diet with lots of fruits and vegetables.
• Get regular exercise.
• Avoid smoking or using tobacco products.
• Avoid secondhand smoke.
• Avoid excess sun exposure and always wear sunscreen, a hat and protective clothing when out in the sun.

Ataxia-telangiectasia care at St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer and to improve the care and treatment for patients who are affected by these conditions.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

• A complete health history
• A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
• Physical exams to check for genetic disease
• Confidential genetic counseling and testing
• Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
• Recommended cancer treatments and ways to reduce cancer risk
• Genetic testing for immediate (1st degree) relatives
  

A-T increases your child’s risk for several types of cancer. Visit Diseases Treated to learn more about how we treat specific cancer types.

St. Jude is also home to the Pediatric Transitional Neuroscience Initiative (PTNI). It brings the mission of St. Jude to children living with certain neurological disorders, including A-T. PTNI brings together scientists, leading medical providers, patient advocates, and others to address the unmet needs of children with these disorders. The Center for Experimental Neurotherapeutics (CENT) was established as part of PTNI to move the most promising experimental therapies from lab into clinical tests as soon as possible.

Related clinical trials 

St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancers associated with A-T.

Learn more about clinical research at St. Jude.

If you have questions about the Genetic Predisposition Clinic and care for A-T, email our team at GPTeam@stjude.org.

Resources outside St. Jude