Ataxia-Telangiectasia, Louis-Bar Syndrome

Abstract

Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is characterized by cerebellar ataxia, cutaneomucosal telangiectasias (small dilated blood vessels), immune defects, and a predisposition to malignancy. The severity of the neurological, immune system and pulmonary manifestations is variable. The onset occurs between age 1 and 2 years with abnormal head movements, loss of balance, slurred speech, and abnormal eye movements. Poor coordination and trembling of the extremities may appear towards 9–10 years of age and worsen progressively. Choreoathetosis is quite common. About 30 % of patients have learning difficulties or moderate intellectual deficiency. Telangiectasias appear between 3 and 6 years of age, or during adolescence. The immunodeficiency causes repeated sinus and lung infections, and the latter may cause bronchiectasis. Growth delay is also fairly frequent. Chromosomal breakage is a feature of the disease; affected cells are abnormally sensitive to killing by ionizing radiation and abnormally resistant to inhibition of DNA synthesis by ionizing radiation. The disease is associated with mutations in the ATM gene (Table 80.1), which is expressed ubiquitously and encodes a protein kinase playing a key role in the control of double-strand-break DNA repair, notably in the Purkinje cells of the cerebellum and in cerebral, cutaneous, and conjunctival endothelial cells.