Department of Neurology, University of Chicago Biological Sciences Division, Chicago, Illinois, USA.
Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, California, Los Angeles, USA.
Ann Neurol. 2024 Dec;96(6):1092-1103. doi: 10.1002/ana.27060. Epub 2024 Sep 12.
Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.
We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B.
In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine.
Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024;96:1092-1103.
由于成纤维细胞生长因子 14（FGF14）基因中的 GAA 重复扩展，新近认识到脊髓小脑性共济失调 27B（SCA27B）是导致晚发性遗传性小脑性共济失调的常见原因。在此，我们报告了首例该病的美国人群病例，描述了其临床表现、疾病进展、病理学异常以及对 102 例携带 GAA 重复扩展患者使用 4-氨基吡啶的反应。
我们从美国 5 个学术中心收集了一系列 SCA27B 患者，采用不设盲的方式，根据标准化表格，回顾性地从临床记录中收集临床表现和患者人口统计学资料。对 4 例经基因证实的 SCA27B 患者进行了尸检分析。
在我们的 SCA27B 患者队列中，我们发现 SCA27B 是一种晚发性（57±12.5 岁）、缓慢进展性共济失调，51%的患者存在发作性成分。平衡和步态障碍几乎总是在疾病发作时出现。4 例脑标本尸检的主要发现是浦肯野神经元丢失，在前小脑蚓部最严重，特别是在前小脑蚓部。与欧洲人群相似，28 例患者中有 21 例（75%）报告 4-氨基吡啶治疗有阳性反应。
我们的研究进一步估计了 SCA27B 的患病率，并进一步扩展了该病的临床表现、影像学和病理学特征，同时观察了该病患者的治疗反应、疾病进展和生存情况。应考虑在所有未确诊的共济失调患者中进行 SCA27B 检测，尤其是那些有发作性起病的患者。神经病学 2024；96：1092-1103。
