ABSTRACT

Introduction: Although one of the most common monogenic late-onset neurodegenerative disorders, fragile-X-associated tremor/ataxia syndrome (FXTAS) is still underdiagnosed. The aim of the present study was to estimate the frequency of premutation carriers in patients with unexplained degenerative ataxias, action tremor or parkinsonism, and action tremor with or without associated cognitive impairment.

Methods: The study comprised 100 consecutive patients with the disease onset >49 years who had any form of unexplained action tremor, cerebellar ataxia, followed by parkinsonism with or without incipient dementia, and in whom the FMR1 repeats size was determined.

Results: Premutation in the FMR1 was identified in two patients (2%): the first, male patient had 83 CGG repeats and the second, female patient had 32 and 58 CGG repeats.

Discussion/Conclusion: FXTAS was relatively rare among older patients with unexplained ataxia and action tremor, with or without parkinsonism and/or cognitive impairment. Tremor and ataxia were major clinical features in our two patients, although parkinsonism, autonomic dysfunction and psychiatric problems might be an important part of the spectrum. Probable FXTAS should be considered in the differential diagnosis of patients with unexplained action tremor and ataxia, and undetermined parkinsonism, especially when there was a positive family history for involuntary movement disorders in other family members and/or autism spectrum disorders in younger cousins.

摘要

简介：尽管是最常见的单基因迟发性神经退行性疾病之一，但脆性X相关震颤/共济失调综合征（FXTAS）仍未得到充分诊断。本研究的目的是评估患有无法解释的退行性共济失调，行动性震颤或帕金森症以及行动性震颤伴或不伴有相关认知障碍的患者的突变前携带者的频率。

方法：该研究纳入了100例疾病发作时间超过49岁的患者，这些患者患有任何形式的无法解释的动作性震颤，小脑性共济失调，然后伴或不伴早期痴呆的帕金森病，并确定了FMR1重复的大小。

结果：在两名患者（2％）中发现了FMR1的突变，第一个是男性患者，有83个CGG重复，第二个，女性患者，有32和58个CGG重复。

讨论/结论：FXTAS在患有无法解释的共济失调和动作震颤，伴或不伴帕金森氏症和/或认知障碍的老年患者中相对较少。震颤和共济失调是这两名患者的主要临床特征，尽管帕金森病，自主神经功能障碍和精神病可能是这一范围的重要组成部分。在无法解释的动作性震颤和共济失调，帕金森病不确定的患者的鉴别诊断中，应考虑可能的FXTAS，特别是当其他家庭成员的非自愿性运动障碍和/或年轻表亲的自闭症谱系存在阳性家族史时。