Ataxia telangiectasia natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Natural History
The outlook for AT sufferers is not good, mainly due to the compromised immune system which results in recurrent respiratory infections. Neurological features are progressive as is deterioration and aging of the skin and hair with ataxia usually seen in the first year of life. Sufferers are usually wheelchair bound by the age of 10 or 11. Telangiectasias are not seen in the early stages of the disease and begin to appear after a few years i.e. between 3-6 years of age, in the corners of the eyes, ears and cheeks. Individuals are also at a 10% risk of developing cancer, usually lymphomas and often breast cancer. However due to sufferers hyper-sensitivity to ionising radiation, radiotherapy and chemotherapy must be used with extreme caution. Oculo-cutaneous telangiectasia is often not obvious in the early stages of the disease. Other features of the disease may include mild diabetes mellitus, premature graying of the hair, difficulty swallowing, and delayed physical and sexual development. People with the disease usually have normal intelligence. Mental retardation is uncommon in people with A-T.[1]
Complications
Carriers of any type of ATM mutation have a 5-8 fold increased risk of cancer and on average die 7-8 years earlier than the normal population, often from heart disease. Individuals with a single ATM mutation are also at a higher risk from lung, gastric and lymphoid tumours, as well as breast cancer. S707P is known to be particularly common in breast cancer patients and F1463S is known to be associated with Hodgkin’s lymphoma. A recent study suggests that the majority of AT sufferers die from pulmonary infections (46%), with 21% dying from malignancies and 28% from malignancies and pulmonary infection. If pulmonary infections could be completely eradicated AT is consistent with survival into the 5th or 6th decade.
Prognosis
The prognosis for AT sufferers is not good. Those with the disease usually die in their teens or early 20s although some individuals have been know to live to over 40. Carriers of ATM missense mutations are believed to have a 60% penetrance by age 70 and a risk of breast cancer 16x that of the normal population. Some papers state a lifetime risk for people with both null and missense mutations of 10-38%, which is still a hundred fold increase from population risk.