Wei Shanshan, Zhao Zhe, Li Nan, Guo Xuan, Chen Jiannan, Hu Jing
Department of Neurology, Hebei Medical University Third Hospital, Shijiazhuang, China.
Front Neurol. 2025 Sep 10;16:1661707. doi: 10.3389/fneur.2025.1661707. eCollection 2025.
Spinocerebellar ataxias (SCAs) exhibit substantial clinical and genetic heterogeneity. SCAs primarily present with progressive ataxia as the cardinal clinical feature. However, they may co-occur with non-ataxic motor symptoms, including various movement disorders. Notably, certain SCA subtypes may present with movement disorders as their primary manifestation. This phenotypic complexity poses significant diagnostic challenges, particularly in distinguishing SCAs from other neurodegenerative conditions with overlapping presentations.
This study enrolled 35 probands initially diagnosed with movement disorders. Participants were stratified into hypokinetic movement disorders and hyperkinetic movement disorders groups. After excluding known genetic causes of movement disorders through targeted next-generation sequencing (NGS) panel, negative cases received SCA repeat expansion testing. Genetically confirmed SCA cases received comprehensive clinical-genetic characterization.
Four SCA cases were identified in the hypokinetic movement disorders group ( = 28), accounting for 14.29% (4/28). Notably, an SCA8-associated familial parkinsonism pedigree manifested a novel clinical constellation: Parkinson's disease -like phenotype with spastic paraplegia and levodopa responsive parkinsonism with dystonia. Additionally, we observed: (i) An SCA2 pedigree demonstrating intrafamilial phenotypic heterogeneity; (ii) Two sporadic early-onset parkinsonism cases harboring pathogenic expansions in SCA8 (CTA/CTG 55 repeats) and SCA3, respectively. Two SCA cases were detected in the hyperkinetic movement disorders group ( = 7), representing 28.57% (2/7). We observed: (i) an SCA3 preataxic carrier presenting with Tourette syndrome; (ii) an SCA17 case (CAG/CAA 41 repeats) manifesting dystonia and spastic paraplegia.
We characterized a novel clinical constellation in an SCA8-associated familial parkinsonism pedigree: Parkinson's disease -like phenotype with spastic paraplegia and levodopa responsive parkinsonism with dystonia. We report the first documented occurrence of Tourette syndrome in the pre-ataxic stage of SCA3, though it is more likely a coincidental comorbidity independent of SCA3 progression. Furthermore, our findings indicate that SCA subtypes presenting with movement disorder-dominant phenotypes are likely underestimated in clinical practice.
脊髓小脑共济失调（SCA）表现出显著的临床和遗传异质性。SCA主要以进行性共济失调作为主要临床特征。然而，它们可能与非共济失调性运动症状同时出现，包括各种运动障碍。值得注意的是，某些SCA亚型可能以运动障碍作为主要表现。这种表型复杂性带来了重大的诊断挑战，尤其是在将SCA与其他具有重叠表现的神经退行性疾病区分开来时。
本研究纳入了35例最初被诊断为运动障碍的先证者。参与者被分为运动减少性运动障碍组和运动增多性运动障碍组。通过靶向二代测序（NGS） panel排除已知的运动障碍遗传原因后，阴性病例接受SCA重复扩增检测。基因确诊的SCA病例接受全面的临床-遗传特征分析。
在运动减少性运动障碍组（n = 28）中鉴定出4例SCA病例，占14.29%（4/28）。值得注意的是，一个与SCA8相关的家族性帕金森综合征家系表现出一种新的临床症状组合：类似帕金森病的表型伴痉挛性截瘫以及对左旋多巴有反应的帕金森综合征伴肌张力障碍。此外，我们观察到：（i）一个SCA2家系表现出家族内表型异质性；（ii）两例散发性早发性帕金森综合征病例，分别在SCA8（CTA/CTG 55次重复）和SCA3中存在致病性扩增。在运动增多性运动障碍组（n = 7）中检测到2例SCA病例，占28.57%（2/7）。我们观察到：（i）一名SCA3共济失调前期携带者表现为抽动秽语综合征；（ii）一例SCA17病例（CAG/CAA 41次重复）表现为肌张力障碍和痉挛性截瘫。
我们在一个与SCA8相关的家族性帕金森综合征家系中描述了一种新的临床症状组合：类似帕金森病的表型伴痉挛性截瘫以及对左旋多巴有反应的帕金森综合征伴肌张力障碍。我们报告了首例有记录的SCA3共济失调前期阶段出现抽动秽语综合征的病例，尽管这更可能是一种与SCA3进展无关的巧合性合并症。此外，我们的研究结果表明，在临床实践中，以运动障碍为主导表型的SCA亚型可能被低估了。
