Ataxia Telangiectasia


Ataxia telangiectasia (AT) is the most common form of infantile-onset cerebellar ataxia, with a prevalence estimated at 1-2.5 per 100,000. In the classical form of AT progressive gait unsteadiness begins in the second year of life, soon after beginning to walk. Slurring of speech and hand incoordination follow soon afterward. There may be a history of mild mental delay. Head thrusting movements with voluntary gaze are sometimes seen, arising from a characteristic gaze apraxia. With progressive ataxia, patients are usually wheelchair-bound in childhood. Rarely, milder forms may have age of onset of cerebellar symptoms as late as 9 years of age, or may present with the gaze apraxia and resting tremor along with the systemic signs. AT is systemic condition in which the underlying cellular abnormality is related to defective DNA repair. AT patients have immunological incompetence, increased risk of malignancy, and progeric features. Patients often have a history of chronic sinusitis and bronchiectasis and cutaneous infections, such as impetigo, before the onset of neurological abnormalities. AT patients also have an increased frequency of lymphoreticular malignancy and germ cell tumors in childhood, and adenocarcinoma and other solid tumors as adults. First degree relatives, obligate carriers of the recessively inherited mutation also have an increased incidence of adenocarcinoma. There is often a delay in development of secondary sex characteristics, and a delayed or irregular menstrual cycle, indicating the presence of hypogonadism. There is no specific treatment for AT. Prevention and treatment of infections and early diagnosis and treatment of malignancies have the most significant impact on long-term survival. Because of the marked radiosensitivity of non malignant tissues in AT, tumors should not be treated with radiotherapy.