Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is an autosomal recessive disorder that primarily involves the CNS (particularly the cerebellum), the ocular surface, the skin, and the immune system. Though rare (prevalence is about 1:40,000), AT is thought to be the most common cause of progressive ataxia in early childhood. Truncal ataxia is usually noted during the second year of life, with subsequent development of dysarthria, dystonia, and choreoathetosis. Progressive deterioration of motor function leads to serious disability by age 10 years. Intellectual impairment, if present, is usually mild.
Recognition of ocular features is often the key to diagnosis of AT. Ocular motor abnormalities are found in many patients with AT and are frequently among the earliest manifestations. Characteristically, the ability to initiate saccades with preservation of vestibulo-ocular movements is poor, very similar to congenital ocular motor apraxia. Head thrusts are used to compensate for saccades. Strabismus and nystagmus may also be present.
Telangiectasia of the conjunctiva develops between the ages of 3 and 5 years. In one study, 91% of AT patients had conjunctival telangiectasia. Involvement is initially interpalpebral but away from the limbus, eventually becoming generalized (Fig 27-11). Similar, though less obvious, vessel changes can appear in the skin of the eyelids and other sun-exposed areas. A variety of skin changes that suggest accelerated aging are common in older children and adults with AT.
Individuals with AT show greatly increased sensitivity to the tissue-damaging side effects of therapeutic radiation and many chemotherapeutic agents. Defective T-cell function in patients with AT is usually associated with hypoplasia of the thymus and decreased levels of circulating immunoglobulin. Recurrent respiratory tract infections are a serious problem, frequently causing death in adolescence or young adulthood even with optimal antimicrobial and supportive treatment. The increased susceptibility to various malignancies, particularly lymphomas and leukemias, contributes to early mortality in one-third to one-half of cases.
The causative gene in AT is called ATM (ataxia-telangiectasia mutated gene) and is found on chromosome 11q22.3. The protein of ATM is involved in the repair of DNA and the regulation of tumor suppressor genes, including BRCA1. A new rapid test from peripheral blood can diagnose AT accurately. AT heterozygosity is present in an estimated 1%–3% of the population. Although gene carriers are generally healthy and cannot be identified except in the context of a known AT pedigree, they are at significantly increased risk for common forms of malignancy and show greater-than-normal sensitivity to radiation. In women heterozygous for the AT gene, breast cancer is about 7 times more frequent than in noncarriers and may account for nearly 10% of all cases in the United States.
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