ataxia telangiectasia

Ataxia telangiectasia (AT) is a rare, multi-system neurological and immunologic condition that typically begins in early childhood. It is caused by changes in the ATM gene, which encodes a protein crucial for DNA damage response and cellular repair. Children with AT develop progressive problems with balance and coordination and have visible small blood-vessel dilations (telangiectasias), especially in the eyes and skin. Because ATM also safeguards the immune system and genome stability, affected individuals are prone to recurrent infections and have a markedly increased lifetime risk of certain cancers. The condition affects fewer than 1 in a million people worldwide.

Symptoms usually appear in the first years of life. Early clues include unsteady walking and frequent falls due to cerebellar ataxia, often followed by slurred speech and difficulty with fine motor tasks. By school age, many children develop the tiny red "spider" veins called telangiectasias on the whites of the eyes or sun-exposed skin, a hallmark feature that helps clinicians recognize the disorder. Over time, neurological challenges progress. Tremor, abnormal eye movements such as nystagmus, and involuntary movements (choreoathetosis) may appear, and speech can become more difficult to understand. Most individuals eventually need mobility aids. The immune system is variably affected: low immunoglobulin levels, reduced lymphocyte counts, and thymic underdevelopment contribute to recurrent sinopulmonary infections that can damage the lungs. Additional features can include delayed puberty, premature graying of the hair, elevated liver enzymes, and in females polycystic ovaries. AT also carries a significantly higher risk of malignancies, particularly lymphoid cancers, across childhood and adulthood. Not all individuals experience every feature, and severity varies considerably.

AT results from pathogenic variants in the ATM gene. The ATM protein acts as a master regulator of the cell’s response to DNA breaks; without it, cells accumulate genetic errors, leading to neurodegeneration, immune dysfunction, and cancer susceptibility. The condition is inherited in an autosomal recessive pattern, meaning a child must receive one altered ATM copy from each parent to be affected. Carriers, who have only one altered copy, are usually healthy but can pass the variant to their children. Because AT is rare, it is more likely to occur when parents share a common ancestor, which increases the chance that both carry the same rare variant. Carrier testing and genetic counseling are strongly recommended for family members who may be at risk.

Currently, management focuses on supportive care tailored to each individual’s needs, and typically involves a multidisciplinary team that may include neurologists, immunologists, pulmonologists, oncologists, physical and speech therapists, and genetic counselors. Immunoglobulin replacement therapy can reduce the frequency and severity of infections in those with significant antibody deficiency. Physical and occupational therapy help maintain mobility and optimize daily function, while speech therapy addresses dysarthria and swallowing challenges. When infections occur, prompt antibiotic treatment and, when needed, respiratory support are important. Long-term management also relies on regular surveillance to detect complications early. Recommended monitoring strategies often include periodic pulmonary function testing, annual skin and eye examinations for telangiectasia progression, liver enzyme assessments, and structured cancer surveillance guided by oncology specialists. Because treatment recommendations evolve, individuals and families should review care plans regularly with their healthcare team.

The outlook for people with AT is highly variable and depends on the severity of neurological symptoms, the degree of immune compromise, and the development of malignancies. Some individuals remain ambulatory into adolescence, whereas others require wheelchairs much earlier. Recurrent respiratory infections and cancer pose significant health challenges, but proactive infection control, vigilant cancer monitoring, and advances in medical care have improved quality of life and survival in recent decades. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors to understand individualized risks and to coordinate comprehensive care.

Several clinical trials are currently investigating new treatments, including therapies aimed at enhancing DNA repair pathways, modulating the immune response, or reducing neurological decline. Individuals interested in participating can search ClinicalTrials.gov or consult their care team about eligibility.