The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia

Neurology. 2014 Sep 16;83(12):1087-95. doi: 10.1212/WNL.0000000000000794. Epub 2014 Aug 13.

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 = 0.003), and longer survival (p = 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 α-fetoprotein (AFP) level was normal in 7%, chromosomal instability was found in 29% (vs 100% of typical patients, p = 0.0006), and immunoglobulin deficiency was found in 29% (vs 69%, p = 0.057). All patients exhibited 2 ATM mutations, including at least 1 missense mutation in 79% of them (vs 36%, p = 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Ataxia Telangiectasia / epidemiology
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / physiopathology*
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Chromosomal Instability / genetics
  • Cohort Studies
  • Disease Progression
  • Dysarthria / genetics
  • Dysarthria / physiopathology*
  • Dystonia / genetics
  • Dystonia / physiopathology*
  • Eye Movement Measurements
  • Female
  • Genetic Pleiotropy
  • Humans
  • Immunoglobulins / deficiency
  • Male
  • Mobility Limitation
  • Movement Disorders / genetics
  • Movement Disorders / physiopathology
  • Mutation, Missense
  • Myoclonus / genetics
  • Myoclonus / physiopathology
  • Ocular Motility Disorders / genetics
  • Ocular Motility Disorders / physiopathology
  • Phenotype
  • Severity of Illness Index
  • Young Adult
  • alpha-Fetoproteins

Substances

  • Immunoglobulins
  • alpha-Fetoproteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins