We report the case of a patient with a clinical phenotype characterized by distal lower limb weakness and pes cavus. The electrophysiological study showed slightly reduced or normal amplitude of motor potentials, a decremental response to repetitive nerve stimulation and post‐exercise facilitation. Muscle biopsy showed only mild neurogenic features. Genetic analysis included a clinical exome sequencing, followed by Sanger analysis. Three‐dimensional (3D) models were generated with a SwissModel (https://swissmodel.expasy.org/) to explain the clinical observations and reinforce the pathogenic nature of the genetic variant identified. Genetic analysis demonstrated a new de novo heterozygous in frame deletion of the SYT2 gene (NM_177402.4: c.1082_1096del), confirmed by Sanger sequencing, which removes five aminoacids in the C2B domain of synaptotagmin‐2 protein, that cause a profound effect on the structure and function of this synaptic vesicle protein. We identified a de novo genetic variant in the SYT2 gene, further supporting its association with a highly stereotyped clinical and electrophysiological phenotype. Our case showed electrophysiological features consistent with a presynaptic dysfunction in the neuromuscular junction with normal post‐exercise amplitudes, not supporting the presence of predominant axonal damage. Although the analysis of SYT2 gene should be included in genetic analysis of patients presenting with this clinical phenotype that mimics motor neuropathy, clinicians have to consider the study of neuromuscular transmission to early identify this potentially treatable condition.

中文翻译：

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一种新的新的 SYT2 突变，表现为远端无力。神经病变或神经肌肉接头功能障碍？

我们报告了一名患者的临床表型，其特征是远端下肢无力和 pes cavus。电生理学研究显示运动电位的幅度略有降低或正常，对重复神经刺激和运动后易化的反应减弱。肌肉活检仅显示轻度神经源性特征。遗传分析包括临床外显子组测序，然后是 Sanger 分析。使用 SwissModel (https://swissmodel.expasy.org/) 生成三维 (3D) 模型以解释临床观察结果并加强所鉴定遗传变异的致病性。遗传分析证明了新的SYT2框架缺失的从头杂合基因 (NM_177402.4: c.1082_1096del)，通过 Sanger 测序证实，它去除了突触结合蛋白 2 蛋白 C2B 结构域中的五个氨基酸，这对这种突触小泡蛋白的结构和功能产生了深远的影响。我们在SYT2基因中发现了一个de novo遗传变异，进一步支持其与高度刻板的临床和电生理表型的关联。我们的病例显示电生理特征与运动后振幅正常的神经肌肉接头突触前功能障碍一致，不支持主要轴突损伤的存在。虽然对SYT2的分析 基因应该被包括在表现出这种模仿运动神经病的临床表型的患者的遗传分析中，临床医生必须考虑神经肌肉传递的研究，以及早识别这种潜在的可治疗疾病。