Ataxia Telangiectasia (AT)—also known as Louis-Bar syndrome, cerebello-oculocutaneous telangiectasia, or immunodeficiency with ataxia telangiectasia—is a rare inherited childhood neurological disorder that affects the part of the brain that controls motor movement (intended movement of muscles) and speech. AT also affects the spine and immune system. It usually begins in early childhood before age 5.

AT is caused by mutations in the ATM (ataxia-telangiectasis mutated) gene. Some children with AT develop cancer, most frequently acute lymphocytic leukemia or lymphoma.

Neurological symptoms include:

• Unsteady walking and lack of balance
• Lack of coordination of movement
• Slurred speech
• Difficulty swallowing
• Unintentional movement, such as tremor or jerky movement
• Difficulty coordinating eye movement

Other symptoms may include:

• Frequent respiratory infections
• Red “spider” veins around the eyes, ears, or cheeks (telangiectasias)
• Increased sensitivity to ionizing radiation (such as X-rays or gamma rays)
• Diabetes
• Premature graying of the hair
• Fatigue
• Delayed physical and sexual development

There is no cure for AT and, currently, no way to slow the progression. Treatment is symptomatic and supportive, such as physical therapy to help maintain flexibility and speech therapy to teach children how to control breathing. Additionally, high-dose vitamins, antioxidants, and gamma-globulin injections may be useful. The severity of the ATM mutation adjusts the average lifespan. Those who had a later onset and slower progression of AT typically survive into their 50s.

Variants (also called mutations) in the ATM gene cause ataxia-telangiectasia. The ATM gene provides instructions for making a protein that helps control cell division and is involved in DNA repair. This protein plays an important role in the normal development and activity of several body systems, including the nervous system and immune system. The ATM protein assists cells in recognizing damaged or broken DNA strands and coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information.

Variants in the ATM gene reduce or eliminate the function of the ATM protein. Without this protein, cells become unstable and die. Cells in the part of the brain involved in coordinating movements (the cerebellum) are particularly affected by loss of the ATM protein. The loss of these brain cells causes some of the movement problems characteristic of ataxia-telangiectasia. Variants in the ATM gene also prevent cells from responding correctly to DNA damage, which allows breaks in DNA strands to accumulate and can lead to the formation of cancerous tumors.

Normal Function

The ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps control the rate at which cells grow and divide. This protein also plays an important role in the normal development and activity of several body systems, including the nervous system and the immune system. Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. DNA can be damaged by agents such as toxic chemicals or radiation. Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information.

Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research.

Health Conditions Related to Genetic Changes

Ataxia-telangiectasia

Researchers have identified several hundred variants (also called mutations) in the ATM gene that cause ataxia-telangiectasia. This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood. People with this disorder have variants in both copies of the ATM gene in each cell. Most of these variants disrupt protein production, resulting in an abnormally small, nonfunctional version of the ATM protein. Cells without any functional ATM protein are hypersensitive to radiation and do not respond normally to DNA damage. Instead of activating DNA repair, the altered ATM protein allows variants to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. This kind of unregulated cell growth can lead to the formation of cancerous tumors. In addition, ATM gene variants can allow cells to die inappropriately, particularly affecting cells in a part of the brain involved in coordinating movements (the cerebellum). This loss of brain cells causes the movement problems characteristic of ataxia-telangiectasia.

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Other cancers

Research suggests that people who carry one alterd copy of the ATM gene in each cell may have an increased risk of developing several other types of cancer. In particular, some studies have shown that cancers of the breast, stomach, bladder, pancreas, lung, and ovaries occur more frequently in ATM gene variant carriers than in people who do not carry these variants. The results of similar studies, however, have been conflicting. Additional research is needed to clarify which other types of cancer, if any, are associated with ATM gene variants.

Other Names for This Gene

• AT mutated
• AT protein
• AT1
• ATA
• ataxia telangiectasia mutated
• ATM_HUMAN
• human phosphatidylinositol 3-kinase homolog
• serine-protein kinase ATM
• TEL1
• TELO1

Genomic Location

Ataxia-telangiectasia is inherited in an autosomal recessive pattern, which means both copies of the ATM gene in each cell have variants. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but do not show signs and symptoms of the condition.

About 1 percent of the United States population carries one altered copy and one normal copy of the ATM gene in each cell. These individuals are called carriers. Although ATM gene variant carriers do not have ataxia-telangiectasia, they are more likely than people without an ATM gene variant to develop cancer; female carriers are particularly at risk for developing breast cancer. Carriers of a variant in the ATM gene also may have an increased risk of heart disease.

Ataxia-telangiectasia occurs in 1 in 40,000 to 100,000 people worldwide.