The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia

Abstract

Objective: To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders. Methods: A total of 14 consecutive adults with A-T were included at 2 tertiary adult movement disorders centers and compared to 53 typical patients with A-T. Clinical evaluation, neurophysiologic and video-oculographic recording, imaging, laboratory investigations, and ATM analysis were performed. Results: In comparison with typical A-T cases, our patients demonstrated later mean age at onset (6.1 vs 2.5 years, p , 0.0001), later loss of walking ability (p 5 0.003), and longer survival (p 5 0.0039). The presenting feature was ataxia in 71%and dysarthria and dystonia in 14%each. All patients displayed movement disorders, among which dystonia and subcortical myoclonus were the most common (86%), followed by tremor (43%). Video-oculographic recordings revealed mostly dysmetric saccades and 46%of patients had normal latencies (i.e., no oculomotor apraxia) and velocities. The a-fetoprotein (AFP) level was normal in7%, chromosomal instability was found in 29% (vs 100% of typical patients, p 5 0.0006), and immunoglobulin deficiency was found in 29%(vs 69%, p 5 0.057). All patients exhibited 2 ATM mutations, including at least 1 missense mutation in 79% of them (vs 36%, p 5 0.0067). Conclusion: There is great variability of phenotype and severity in A-T, including a wide spectrum of movement disorders. Karyotype and repeated AFP level assessments should be performed in adults with unexplained movement disorders as valuable clues towards the diagnosis. In case of a compatible phenotype, A-T should be considered even if age at onset is late and progression is slow.