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

The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia.

Author information

1
From INSERM, UMRS 975, CNRS 7225-CRICM (A.M., E.A., S.R.-P., A.D., M.V., D.G.), AP-HP, Fédération de Neurophysiologie Clinique (B.G., T.M.), AP-HP, Département des Maladies du Système Nerveux (B.D., M.V., D.G.), Département de Génétique et Cytogénétique, Unité Fonctionnelle de Génétique Chromosomique (B.B.), and Département de Génétique et Cytogénétique (A.D., M.A.), Hôpital Pitié-Salpêtrière, Paris; Université Pierre et Marie Curie-Paris-6 (A.M., B.G., E.A., S.R.-P., B.D., A.D., M.V., D.G.); AP-HP, Service de Physiologie (Y.A.-B., E.A.), Hôpital Saint-Antoine; INSERM U830 (G.R., M.-H.S., D.S.-L.), Paris; Unité d'Immuno-Hématologie et Rhumatologie Pédiatriques (N.M., A.F.), CEREDIH (French Reference Center for Primary Immunodeficiencies) (N.M., F.S., A.F.), and Service d'Hématologie Adultes (F.S.), Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP); Imagine Institute (N.M., F.S., A.F.), Sorbonne Paris Cité (D.S.-L.), Université Paris Descartes; Département de Neurologie (C.T., M.A.), Hôpital Civil de Strasbourg; Fédération de Médecine Translationnelle de Strasbourg (FMTS) (C.T., M.A.), Université de Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (C.T., M.K., M.A.), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch; Laboratoire de Diagnostic Génétique (M.K.), Nouvel Hôpital Civil, Strasbourg; Laboratoire de Génétique des Maladies Rares (M.K.), INSERM UMR_S 827, Institut Universitaire de Recherche Clinique, Montpellier; and Department of Tumour Biology (M.-H.S., C.D.E., D.S.-L.), Institut Curie, Paris, France.
2
From INSERM, UMRS 975, CNRS 7225-CRICM (A.M., E.A., S.R.-P., A.D., M.V., D.G.), AP-HP, Fédération de Neurophysiologie Clinique (B.G., T.M.), AP-HP, Département des Maladies du Système Nerveux (B.D., M.V., D.G.), Département de Génétique et Cytogénétique, Unité Fonctionnelle de Génétique Chromosomique (B.B.), and Département de Génétique et Cytogénétique (A.D., M.A.), Hôpital Pitié-Salpêtrière, Paris; Université Pierre et Marie Curie-Paris-6 (A.M., B.G., E.A., S.R.-P., B.D., A.D., M.V., D.G.); AP-HP, Service de Physiologie (Y.A.-B., E.A.), Hôpital Saint-Antoine; INSERM U830 (G.R., M.-H.S., D.S.-L.), Paris; Unité d'Immuno-Hématologie et Rhumatologie Pédiatriques (N.M., A.F.), CEREDIH (French Reference Center for Primary Immunodeficiencies) (N.M., F.S., A.F.), and Service d'Hématologie Adultes (F.S.), Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP); Imagine Institute (N.M., F.S., A.F.), Sorbonne Paris Cité (D.S.-L.), Université Paris Descartes; Département de Neurologie (C.T., M.A.), Hôpital Civil de Strasbourg; Fédération de Médecine Translationnelle de Strasbourg (FMTS) (C.T., M.A.), Université de Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (C.T., M.K., M.A.), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch; Laboratoire de Diagnostic Génétique (M.K.), Nouvel Hôpital Civil, Strasbourg; Laboratoire de Génétique des Maladies Rares (M.K.), INSERM UMR_S 827, Institut Universitaire de Recherche Clinique, Montpellier; and Department of Tumour Biology (M.-H.S., C.D.E., D.S.-L.), Institut Curie, Paris, France. mathieu.anheim@chru-strasbourg.fr.

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.

PMID:
25122203
DOI:
10.1212/WNL.0000000000000794
[Indexed for MEDLINE]

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