成人共济失调毛细血管扩张症的多效运动障碍表型。
The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia.
机构信息
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.
出版信息
Neurology. 2014 Sep 16;83(12):1087-95. doi: 10.1212/WNL.0000000000000794. Epub 2014 Aug 13.
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.
目的
评估成人共济失调毛细血管扩张症（A-T）的临床谱，重点关注运动障碍。
方法
在 2 家三级成人运动障碍中心共纳入 14 例连续的 A-T 成人患者，并与 53 例典型 A-T 患者进行比较。进行临床评估、神经生理和视频眼动记录、影像学、实验室检查和 ATM 分析。
结果
与典型 A-T 病例相比，我们的患者发病年龄较晚（平均 6.1 岁 vs 2.5 岁，p<0.0001），丧失行走能力较晚（p=0.003），且生存期更长（p=0.0039）。首发症状为共济失调（71%）、构音障碍和肌张力障碍（各 14%）。所有患者均存在运动障碍，其中以肌张力障碍和皮质下肌阵挛最常见（86%），其次是震颤（43%）。视频眼动记录显示，多数为不精准的扫视，46%的患者潜伏期（即眼运动失用症无异常）和速度正常。7%的患者甲胎蛋白（AFP）水平正常，29%的患者存在染色体不稳定性（与典型患者的 100%相比，p=0.0006），29%的患者存在免疫球蛋白缺乏（与 69%相比，p=0.057）。所有患者均存在 2 个 ATM 突变，其中 79%至少存在 1 个错义突变（与 36%相比，p=0.0067）。
结论
A-T 的表型和严重程度存在很大差异，包括广泛的运动障碍谱。对于不明原因运动障碍的成人，应进行核型和反复 AFP 水平评估，这是有价值的诊断线索。如果表型相符，即使发病年龄晚、进展缓慢，也应考虑 A-T。
Zotero 插件