Abstract：
BACKGROUND: Autosomal-dominant spinocerebellar ataxia (ADCA) due to intronic GAA repeat expansion in FGF14 (SCA27B) is a recent, relatively common form of late-onset ataxia.
OBJECTIVE: Here, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies.
METHODS: We screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases.
RESULTS: In our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62 years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment.
CONCLUSIONS: Patients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.
OBJECTIVE: Here, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies.
METHODS: We screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases.
RESULTS: In our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62 years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment.
CONCLUSIONS: Patients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.
摘要：
背景：由于FGF14（SCA27B）的内含子GAA重复扩增而导致的常染色体显性脊髓小脑共济失调（ADCA）是最近的，迟发性共济失调的相对常见形式。
目标：这里，我们的目的是:(1)调查在意大利16个三级研究中心收集的不同临床定义的晚发性共济失调疾病亚组中SCA27B的相对频率;(2)描述SCA27B患者的表型和诊断结果;(3)将意大利队列与最近研究报告的其他队列进行比较.
方法：我们筛选了396例临床诊断为不明原因的晚发性小脑共济失调，细分为散发性小脑共济失调，ADCA,多系统萎缩小脑型。我们用SCA27B鉴定了72名新的遗传定义受试者。然后，我们分析了临床，神经生理学，64例有症状病例的影像学特征。
结果：在我们的队列中，ADCA中SCA27B的患病率为13.4%(53/396),高达38.5%(22/57).SCA27B患者的中位发病年龄为62岁。所有有症状的个体均显示出平衡和步态受损的证据；小脑眼运动体征也很常见。31％的患者在发病时出现了偶发性表现。还报告了锥体外系特征（17％）和认知障碍（25％）。在大多数情况下（78％），脑磁共振成像显示小脑萎缩。伪纵向评估表明共济失调进展缓慢，功能损害最小。
结论：意大利的SCA27B患者以成人起病，缓慢进行性小脑共济失调，主要是轴向受累和频繁的小脑眼运动体征。SCA27B队列在多个人群中的临床特征的高度一致性为大规模，多中心研究。
目标：这里，我们的目的是:(1)调查在意大利16个三级研究中心收集的不同临床定义的晚发性共济失调疾病亚组中SCA27B的相对频率;(2)描述SCA27B患者的表型和诊断结果;(3)将意大利队列与最近研究报告的其他队列进行比较.
方法：我们筛选了396例临床诊断为不明原因的晚发性小脑共济失调，细分为散发性小脑共济失调，ADCA,多系统萎缩小脑型。我们用SCA27B鉴定了72名新的遗传定义受试者。然后，我们分析了临床，神经生理学，64例有症状病例的影像学特征。
结果：在我们的队列中，ADCA中SCA27B的患病率为13.4%(53/396),高达38.5%(22/57).SCA27B患者的中位发病年龄为62岁。所有有症状的个体均显示出平衡和步态受损的证据；小脑眼运动体征也很常见。31％的患者在发病时出现了偶发性表现。还报告了锥体外系特征（17％）和认知障碍（25％）。在大多数情况下（78％），脑磁共振成像显示小脑萎缩。伪纵向评估表明共济失调进展缓慢，功能损害最小。
结论：意大利的SCA27B患者以成人起病，缓慢进行性小脑共济失调，主要是轴向受累和频繁的小脑眼运动体征。SCA27B队列在多个人群中的临床特征的高度一致性为大规模，多中心研究。
