Ataxia Telangiectasia

Clinical Features

Ataxia Telangiectasia (A-T) is characterized by early onset (1-4 years) progressive cerebellar ataxia, telangiectasias of the conjunctivae, oculomotor apraxia, choreoathetosis, immunodeficiency, slurred speech, frequent infections, and an increased risk of cancers, especially leukemia and lymphoma. Other solid tumors do occur. Cancer risk is increased by 60-180 fold over population risk (Thoms et al. 2007. PubMed ID: 17518994). Other features can include premature aging (e.g. grey hair) and insulin-resistant diabetes mellitus. Individuals with A-T are usually sensitive to ionizing radiation (e.g. radiotherapy). Non-classic forms can occur with adult-onset A-T and A-T with early-onset dystonia. Unlike A-T, which is caused by homozygous or compound heterozygous mutations in the ATM gene, heterozygous carriers of an ATM causative mutation are at an increased risk of breast cancer (Concannon et al. 2008. PubMed ID: 18701470) and heart disease (Swift et al. 1991. PubMed ID: 1961222). The time of onset and progression is variable between and within families of affected individuals. The prevalence of A-T has been reported to be 1:40,000-100,000 in the United States (Gatti, R., GeneReviews. 2010; ncbi.nlm.nih.gov/books/NBK26568).

Prevention

Given the cancer predisposition, as well as degenerating muscle and neurologic disorders that accompany A-T, early detection is paramount for therapies and screening (Spacey et al. 2000. PubMed ID: 10975530).

Physical Therapy

Studies show that the single most important supportive therapy for A-T patients is aggressive physical therapy (Spacey et al. 2000. PubMed ID: 10975530). Early and continued physical therapy has been proven to slow muscle degeneration and minimize contractures and scoliosis (Gatti, R., GeneReviews. 2010; ncbi.nlm.nih.gov/books/NBK26468).

Intravenous Immunoglobulin (IVIG) Treatment

Since the greatest mortality to A-T patients is caused by sino-pulmonary infections, prompt treatment with antibiotics as well as IVIG treatment is highly recommended (Spacey et al. 2000. PubMed ID: 10975530).

Studies done on IVIG have shown that it is an effective management option for various autoimmune disorders and has helped some A-T patients avoid fatal complications (Pujal et al. 1999. PubMed ID: 10325463).

Radiation Avoidance

Ionizing radiation, such as CT scans, myo- and neurotoxic agents, and topoisomerase inhibitors should be avoided due to their link to an increase in cancer malignancies (Spacey et al. 2000. PubMed ID: 10975530). The lifetime cancer incidence in affected patients is 10-30%. Awareness and avoidance are key in avoiding morbidity/mortality (Lavin et al. 2007. PubMed ID: 17586848).

Breast Cancer Screening

Through molecular genotyping, it has been proven that A-T heterozygotes (carriers) are predisposed to breast cancer (Athma et al. 1996. PubMed ID: 8976369). Studies have proven that early staged cancer may be less aggressive, and cancer that is detected early generally allows patients to live longer, require less extensive treatment, and fare better (Jotwani and Gralow. 2009. PubMed ID: 19925032). Genetic testing can be useful in identifying at risk family members.

For more information on ATM testing, please see our full Test Description.


Disclaimer

This article is a summary of information that has been reported in the biomedical research literature. It is not medical advice for patients. All disease treatments should be under the direction of a qualified healthcare provider.

Last Updated: 1/25/2018