Definition
Ataxia telangiectasia (A-T, OMIM #208900) is a disease which belongs to the group of DNA repair defects that play an important role in the regulation of central proteins of the signaling cascade between the identification and repair of DNA damage, including the tumor suppressor proteins p53, BRCA1, CHEK2, and NBS1. A-T is characterized by an increased sensitivity to ionizing radiation and by progressive neurological symptoms. NHL and ALL are of primary importance when it comes to a predisposition to cancer.
Key Data
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| Synonym | A-T |
| Gene | ATM (Ataxia telangiectasia mutated) |
| Gene product | Phosphatidylinsositol 3-kinase (PI3) protein family |
| Function | ATM kinase. The ATM mutation leads to a down-regulation of ATM kinase expression and function, resulting in a faulty DNA repair signaling cascade and an accumulation of DNA strand breaks, and results in genetic instability, specifically following exposure to ionizing radiation. |
| Heredity | Autosomal recessive |
| Prevalence | 1:40.000-1:100.000 |
| Genotype-phenotype correlation | c.5762-1050A>G slow neurological progression, later manifestation, intermediate radiosensitivity, risk of cancer increased slightly or not at all c.1A>G, c.7271T>G, c.8147T>C, c.8494C>T, etc. mild phenotype, longer survival, increased risk of cancer |
| Penetrance | High. Onset of initial neurological symptoms at the age of 2-4; most children need a wheelchair at 10 years of age. |
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Diagnosis
Indicative Findings
Confirming the Diagnosis
Differential Diagnoses
Clinical Presentation
Typical A-T
Atypical A-T
Other Findings
Associated Predisposition to Tumors
Therapeutic Considerations
Avoid/reduce exposure to ionizing radiation and X-ray examinations if clinically acceptable.
The treatment of any neoplasia should be adjusted accordingly (reduced doses, longer treatment intervals) due to increased therapeutic toxicity, especially in children.
It is strongly recommended to test the parents whenever A-T is newly diagnosed, since there is also an increased risk of cancer in heterozygous carriers.
Surveillance Recommendations
Surveillance Recommendations
Evidence-based standards are lacking for tumor screening, particularly during childhood. The following are the recommendations from the AACR consensus meeting in October 2016.
