CharlevoixSaguenay常染色体隐性遗传性痉挛性共济失调(ARSACS)现在越来越多地来自世界各国,可能使其成为最常见的常染色体隐性共济失调之一。这里,我们选择了有SACS变异的患者,ARSACS的致病基因,在2019年5月至2021年5月招募的137例早发性共济失调患者的大队列中,患者被转诊至共济失调诊所.对137例患者中的111例(81%)进行了遗传研究,诊断率为72.9%(111例中的81例)。确定了10例分子诊断为ARSACS的患者。我们调查了所有确诊的ARSACS患者的表型和成像光谱。我们还估计了该队列中ARSACS的频率,并描述了他们的临床和遗传发现,包括七个新的变异以及新的神经影像学发现。虽然ARSACS的经典临床三联症是进行性小脑共济失调,痉挛,和感觉运动多神经病,这并不是所有患者的恒定特征。在我们所有的患者中都检测到感觉运动轴索脱髓鞘神经病,但50%(5/10)没有痉挛和伸肌足底反射。在所有患者中,脑磁共振成像(MRI)显示脑桥(脑桥条纹)和前上小脑萎缩以及丘脑周围的高强度边缘(丘脑边缘)。虽然早期ARSACS报道了幕下蛛网膜囊肿,我们首次报道了两名患者的颞叶蛛网膜囊肿,提示蛛网膜囊肿可能是ARSACS的相关影像学特征。我们还通过提供8个致病性和一个未知意义的变异(VUS)序列变异来扩展ARSACS的分子谱,其中7个以前没有报道过。MetaDome服务器证实,鉴定的VUS变体在由SACS编码的sacsin蛋白的不耐受区域中。
Autosomal recessive spastic ataxia of Charlevoix Saguenay (
ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for
ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of
ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with
ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in
ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS.