National Ataxia Clinic, Department of Neurology, Tallaght University Hospital, Tallaght, Dublin 24, Ireland.
School of Medicine, Trinity College Dublin, Dublin, Ireland.
J Neurol. 2021 Oct;268(10):3897-3907. doi: 10.1007/s00415-021-10507-8. Epub 2021 Mar 27.
Mutations in SPG7 are increasingly identified as a common cause of spastic ataxia. We describe a cohort of Irish patients with recessive SPG7-associated phenotype.
Comprehensive phenotyping was performed with documentation of clinical, neurophysiological, optical coherence tomography (OCT) and genetic data from individuals with SPG7 attending two academic neurology units in Dublin, including the National Ataxia Clinic.
Thirty-two symptomatic individuals from 25 families were identified. Mean age at onset was 39.1 years (range 12-61), mean disease duration 17.8 years (range 5-45), mean disease severity as quantified with the scale for the assessment and rating of ataxia 9/40 (range 3-29). All individuals displayed variable ataxia and spasticity within a spastic-ataxic phenotype, and additional ocular abnormalities. Two had spasmodic dysphonia and three had colour vision deficiency. Brain imaging consistently revealed cerebellar atrophy (n = 29); neurophysiology demonstrated a length-dependent large-fibre axonal neuropathy in 2/27 studied. The commonest variant was c.1529C > T (p.Ala510Val), present in 21 families. Five novel variants were identified. No significant thinning of average retinal nerve fibre layer (RNFL) was demonstrated on OCT (p = 0.61), but temporal quadrant reduction was evident compared to controls (p < 0.05), with significant average and temporal RNFL decline over time. Disease duration, severity and visual acuity were not correlated with RNFL thickness.
Our results highlight that recessive SPG7 mutations may account for spastic ataxia with peripheral neuropathy in only a small proportion of patients. RNFL abnormalities with predominant temporal RNFL reduction are common and OCT should be considered part of the routine assessment in spastic ataxia.
SPG7 突变越来越多地被认为是痉挛性共济失调的常见原因。我们描述了一组爱尔兰的隐性 SPG7 相关表型患者。
对在都柏林的两个学术神经内科单位（包括国家共济失调诊所）就诊的 SPG7 患者进行了全面的表型分析，并记录了临床、神经生理学、光学相干断层扫描（OCT）和遗传数据。
从 25 个家族中确定了 32 名有症状的个体。发病年龄的平均值为 39.1 岁（范围 12-61 岁），平均病程为 17.8 年（范围 5-45 年），采用共济失调评估和评分量表（9/40）量化的平均疾病严重程度为 9/40（范围 3-29）。所有个体均表现为痉挛性共济失调表型中的可变共济失调和痉挛，以及其他眼部异常。有 2 人患有痉挛性发音障碍，3 人有色觉缺陷。脑部影像学检查均显示小脑萎缩（n=29）；神经生理学研究显示 2/27 例研究存在长度依赖性大纤维轴索性神经病。最常见的变异是 c.1529C>T（p.Ala510Val），存在于 21 个家族中。发现了 5 个新的变体。OCT 显示平均视网膜神经纤维层（RNFL）无明显变薄（p=0.61），但与对照组相比，颞象限减少（p<0.05），平均和颞 RNFL 随时间显著下降。疾病持续时间、严重程度和视力与 RNFL 厚度无关。
我们的结果表明，隐性 SPG7 突变可能仅导致一小部分患者出现伴周围神经病的痉挛性共济失调。RNFL 异常以颞侧 RNFL 减少为主很常见，OCT 应作为痉挛性共济失调常规评估的一部分。
