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Ataxia-Telangiectasia Factsheet

Published October 2013 NCHPEGAll rights reserved

Clinical featuresAtaxia Telangiectasia (AT) is a rare inherited disorder that affects the nervous, immune, and other body systems. Individuals with AT

have progressive difficulty with coordinating movements (ataxia) beginning in early childhood, usually before age 5. Affected

children typically develop difficulty walking, problems with balance and hand coordination, chorea, myoclonus, and neuropathy.

Most children require a wheelchair by adolescence. People with AT also have slurred speech and oculomotor apraxia.

Telangiectasias often occur in the eyes and on the surface of the skin and are often present in early childhood.

People with AT often have a weakened immune system, and many develop chronic lung infections. They are also at an increased risk

of developing cancer, particularly leukemia and lymphoma. Affected individuals are very sensitive to the effects of radiation

exposure, including medical x-rays. Although people with AT usually live into adulthood, their life expectancy is reduced.

Diagnosis

Diagnosis of AT can be made through immunoblotting of the ATM protein or molecular genetic analysis. Generally, immunoblotting

is used for diagnosis, because of high sensitivity and specificity and lower cost than other testing modalities.

Genetics

AT is caused by variants in the ATM gene, which is normally involved in DNA repair.

Inheritance

AT inherited in an autosomal recessive pattern. Parents of an affected individual are obligate carriers of a single mutation. Siblings of

an affected individual have a 25%, or 1 in 4 chance to have AT, and a 50% chance to be carriers.

Carriers of an ATM mutation are not at risk to develop neurologic manifestations. However, carriers have 4 times the general

population risk for breast cancer, and an increased risk for leukemia. The mechanism of cancer susceptibility in carriers isincompletely understood, but is thought to be related to impaired DNA repair by the ATM protein.

Clinical testing

Immunoblotting for the ATM protein is the most sensitive and specific clinical test for establishing the diagnosis of A-T. Nearly 100%

of individuals with AT will have significantly reduced (usually absent) or non-functional ATM protein. Immunoblotting is also less

expensive than molecular genetic analysis.

Sequencing of the ATM gene identifies a variant in about 90% of affected individuals. Deletion and duplication analysis can identify

variants in an additional 1-2%. However, the effects of a given variant may be difficult to predict, and variants of uncertain clinical

significance are common. Genetic testing fails to identify both disease-causing mutations in about 5-10%. When both ATM variants

have been identified in an affected individual, testing for carrier status is available for relatives. Prenatal testing may also be

available.

Additional clinical testing such as serum AFP assessment and peripheral blood chromosome analysis may show elevated serum AFP

and peripheral blood 7;14 chromosome translocation, respectively. Such findings support the diagnosis of AT.

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Published October 2013 NCHPEGAll rights reserved

Management

Management of AT focuses on treating presenting symptoms, and prevention and surveillance of future manifestations. Treatment

may include intravenous immunoglobulin therapy, physical therapy, and medications to manage neurologic symptoms. Individuals

with AT are monitored for malignancy and should avoid ionizing radiation.

References

GeneReviews: Ataxia-Telangiectasia athttp://www.ncbi.nlm.nih.gov/books/NBK26468/

Genetics Home Reference: Ataxia-Telangiectasia athttp://ghr.nlm.nih.gov/condition/ataxia-telangiectasia

National Institute of Neurological Disorders and Stroke: NINDS Ataxia Telangiectasia Information Page athttp://www.ninds.nih.gov/disorders/a_t/a-t.htm

A-T Childrens Project athttp://www.atcp.org/

http://www.ncbi.nlm.nih.gov/books/NBK26468/http://www.ncbi.nlm.nih.gov/books/NBK26468/http://www.ncbi.nlm.nih.gov/books/NBK26468/http://ghr.nlm.nih.gov/condition/ataxia-telangiectasiahttp://ghr.nlm.nih.gov/condition/ataxia-telangiectasiahttp://ghr.nlm.nih.gov/condition/ataxia-telangiectasiahttp://www.ninds.nih.gov/disorders/a_t/a-t.htmhttp://www.ninds.nih.gov/disorders/a_t/a-t.htmhttp://www.atcp.org/http://www.atcp.org/http://www.atcp.org/http://www.atcp.org/http://www.ninds.nih.gov/disorders/a_t/a-t.htmhttp://ghr.nlm.nih.gov/condition/ataxia-telangiectasiahttp://www.ncbi.nlm.nih.gov/books/NBK26468/