The incidence of AT is between 1-9 in 100,000 live births. This number varies depending on the degree of consanguinity (union between two individuals who are second cousins or closer). For example, the incidence is higher in the North African Jewish population. Males and females are affected equally.

AT is caused by mutations in the ATM gene which encodes a protein with the same name. The ATM protein has a number of functions, but most importantly, it is involved in the regulation of the cell cycle in response to DNA damage. DNA has a double-stranded structure, meaning that two long strands come together and coil around one another. A certain type of DNA damage is a double-stranded break, which is when the bonds in both DNA strands are broken. ATM is involved in stopping the cell cycle when this happens by recruiting other proteins to prevent the proliferation of the cell with damaged DNA.

The mechanism causing ataxia and progressive nerve cell damage and gradual cell death in the brain is not fully understood. Multiple mechanisms have been suggested. It is possible that a mutated ATM cannot respond effectively to chemical stressors that damage the DNA in nerve cells, leading to their destruction and death.

Although the formation of telangiectasia is one of the hallmarks of ATM, the mechanism by which they develop is not known.

ATM is also associated with sensitivity to radiation. This is because radiation tends to cause double-stranded breaks among other forms of DNA damage. In the absence of a fully functional ATM, these double-stranded breaks accumulate and cannot be repaired which causes cell damage. In addition, since ATM cannot effectively stop the cell cycle when double-stranded breaks occur, cells with damaged DNA can proliferate which could eventually lead to cancer. 

The immune system is also weakened in AT because the process of immune cell maturation involves the rapid proliferation of white blood cells, a process that may induce double-stranded breaks and relies on double-stranded break repair mechanisms. In the absence of such mechanisms, an inadequate number of white blood cells are formed and the ones that mature may be abnormal and dysfunctional. 

AT is inherited in an autosomal recessive pattern. This means that both parents need to carry at least one copy of the defective gene and pass it onto the affected individual. 

Symptoms of AT vary from severe and early-onset to mild and late-onset. Reduced muscle coordination is typically the first symptom of AT, which presents when the child begins walking. It is noticed as an unstable and wobbly gait, as well as an unstable trunk. Over time, other movement abnormalities develop including involuntary muscle contractions or tremors and jerky movements. Although affected children typically start walking, they often require a wheelchair by adolescence due to progressive ataxia.

Abnormal movement of the eyes may occur such as rapid back and forth movement of the eyes when attempting to focus on an object (nystagmus), an inability to align the eyes when looking at an object (strabismus), and inability to follow objects across the visual field (oculomotor apraxia). This may impact the child’s reading skills as reading requires both focusing and coordinated horizontal eye movements. Lack of coordination in voluntary movement also makes other fine motor skills such as writing and self-feeding challenging.

Muscles involved in speaking, chewing, and swallowing are also affected. This causes slurred speech, drooling, and difficulty swallowing. Difficulty swallowing is also associated with an increased risk of aspirating or drawing food particles into their airways. This increases the risk of respiratory infections and lung damage. In addition, difficulty chewing and swallowing might prolong the mealtime and be too tiring causing the affected child to reduce their food intake which could result in poor growth. 

Another important feature of AT is telangiectasia. These are thread-like red patterns that form most commonly in the white of the eyes, as well as the skin, particularly sun-exposed areas such as the nose and the ears, and sometimes bladder and brain. Telangiectasias first appear between three and six years of age although they may appear later or never appear. They are the result of the widening of small blood vessels. Telangiectasias do not change over time, bleed, or feel itchy or painful. They do not affect vision. 

In addition, AT also affects the immune system. This predisposes affected individuals to sinopulmonary infections. These infections primarily affect the ears, sinuses, and respiratory tract. Recurrent infections among other factors related to AT may damage the lungs and cause chronic lung disease associated with lingering coughs, wheezing, or fluid accumulation in the lungs.

Individuals affected by AT have a much higher risk of developing certain cancers such as lymphomas (cancer of the lymph nodes) and leukemias (cancer of white blood cells). In addition, ATM moderately increases the risk of other cancers including breast, liver, esophageal, and gastric cancers.

Poor growth is another common finding in AT. This may be partly due to poor nutrition due to feeding difficulties, partly due to recurrent infections and hormonal changes such as deficient growth factor.

Premature aging has also been reported in AT. Features include graying hair, and wrinkled, dry skin that may appear during adolescence. There are also reproductive abnormalities such as delayed puberty and early menopause. In some cases, diabetes mellitus may be present which presents with increased thirst and urination, weight loss, and fatigue. 

The diagnosis of AT is usually suspected in individuals who have clinical features such as an unstable gait and trunk, head tilting, slurred speech, and eye movement abnormalities. In addition, telangiectasias which are present in the majority of affected individuals are helpful in increasing diagnostic suspicion. Laboratory tests and brain imaging can support the diagnosis of AT. However, AT is only confirmed by genetic testing.

Blood tests of affected individuals may show elevated serum alpha-fetoprotein. This is a protein that tends to be elevated in the majority of affected individuals. Blood tests may also detect low antibody levels due to immune system deficiency. Magnetic resonance imaging (MRI) of the brain may show shrinkage (atrophy) of certain areas of the brain that are responsible for coordinating movement (cerebellum). This may not be detectable in very young individuals, however, it becomes more prominent over time. However, none of these features are specific to AT and can only support the diagnosis. The definitive diagnosis of AT is only reached through genetic testing and identifying mutations in ATM.

There are no cures or treatments that slow the progress of AT. Treatment is supportive and specific to symptoms. Affected individuals may benefit from occupational and speech therapy as well as physiotherapy to improve muscle strength, feeding, and speaking abilities. Certain antiparkinson or anti-seizure medications can be helpful to some individuals.

Depending on the immune status of the individual, live vaccines which use a weakened form of the organism that causes the disease may be dangerous. However, other forms of immunization can be helpful in reducing the frequency of infection. If infections continue to persist and recur, intravenous immunoglobulin (IVIG) might be beneficial. IVIG is a blood product made up of donors’ antibodies which are immune proteins that can be given intravenously. In addition, antibiotics can reduce exacerbations in individuals with lung dysfunction. Depending on the type of chronic lung disease that is present, some may benefit from medications called bronchodilators that dilate the airways and make breathing easier. 

Individuals who experience difficulty eating can benefit from learning swallowing and chewing techniques. If poor nutrition is a concern, a dietitian may recommend dietary modifications or certain supplements. In severe cases where malnutrition and aspiration are concerns, a G tube can be surgically inserted through the skin into the belly that delivers food directly into the stomach. 

Proper screening for cancer can be lifesaving by allowing early diagnosis and treatment. Some standard cancer treatments may have to be modified since individuals affected by AT are highly sensitive to radiation and cannot tolerate radiation therapy.

The average life expectancy of individuals affected by AT is around 25 years. Individuals with milder forms of the disease may have a much longer life expectancy. Chronic lung disease and cancer are the most common causes of death in AT. 

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