先天性肌无力综合征-25(CMS-25)是由VAMP1基因纯合突变引起的常染色体隐性遗传性神经肌肉疾病。迄今为止,在12例CMS-25中,仅报道了VAMP1基因中的8种等位基因变体。这里,我们报道了一个8岁男孩的运动发育迟缓,轴向低张力,肌病性面部,肌肉无力,斜视,上睑下垂,Carinatum,脊柱侧后凸,关节挛缩,关节松弛,癫痫发作,和复发性肾结石。他还患有喂养困难和反复发作的吸入性肺炎。20个月大的脑磁共振成像显示左局灶性小脑发育不全。遗传分析显示c.202C>T的纯合错义变体(p。Arg68Ter)在VAMP1基因中。开始口服吡啶斯的明治疗,这导致肌肉力量的轻度改善。几个月后加入了沙丁胺醇糖浆,但没有观察到显著的改善。该病例报告提出了新的发现,例如与VAMP1相关的CMS-25中的局灶性小脑发育不全和肾结石症。因此,此病例报告扩展了临床范围。需要进一步的研究来扩大VAMP1相关CMS-25中的基因型-表型相关性。
Congenital myasthenic syndrome-25 (CMS-25) is an autosomal recessive neuromuscular disorder caused by a homozygous mutation in VAMP1 gene. To date, only eight types of allelic variants in VAMP1 gene have been reported in 12 cases of CMS-25. Here, we report on an 8-year-old boy with motor developmental delay, axial hypotonia, myopathic face, muscle weakness, strabismus, ptosis, pectus carinatum, kyphoscoliosis, joint contractures, joint laxity, seizures, and recurrent nephrolithiasis. He also had feeding difficulties and recurrent aspiration pneumonia. Brain magnetic resonance imaging at 20 months of age showed left focal cerebellar hypoplasia. Genetic analysis revealed a homozygous missense variant of c.202C > T (p.Arg68Ter) in the VAMP1 gene. Treatment with oral pyridostigmine was started, which resulted in mild improvement in muscle strength. Salbutamol syrup was added a few months later, but no significant improvement was observed. This case report presents novel findings such as focal cerebellar hypoplasia and nephrolithiasis in VAMP1-related CMS-25. Consequently, this case report extends the clinical spectrum. Further studies are needed to expand the genotype-phenotype correlations in VAMP1-related CMS-25.