远端型遗传性运动神经病的临床和遗传学研究进展

Progress of clinical and genetic research on distal hereditary motor neuropathy

远端型遗传性运动神经病是一组临床和遗传异质性很强的神经变性疾病,主要表现为肢体远端进行性、对称性肌无力和肌萎缩,中年或幼年起病,以下肢起病多见,可出现延髓麻痹症状,个别存在轻度感觉障碍.体检发现腱反射减弱或消失,肌电图检查提示神经源性损害,肌肉活检提示神经源性肌萎缩.随着该病致病基因定位和基因克隆研究日渐深入,研究者发现远端型遗传性运动神经病与蛋白聚集物形成、自噬通路、RNA加工、翻译合成、轴突运输、内质网应激、钙离子通道和神经保护等受损有关.本文对各型远端型遗传性运动神经病的临床与遗传学研究的进展进行综述.

Distal hereditary motor neuropathy(dHMN)is a group of clinically and genetically heterogeneous disorders characterized by progressive distal weakness and atrophy.The onset of dHMN is at mid adulthood or early childhood,and the symptoms are mainly present in the lower limbs.Besides weakness and atrophy of distal limb muscles,some patients may develop bulbar paralysis,and some may also present with mild sensory disturbance.Decreased or absent tendon reflexes may be discovered.Electromyography may show neurogenic damages.Muscular biopsy may reveal neurogenic amyotrophy.An increasing number of genes have been associated with dHMN.Pathogenesis of dHMN may include formation of protein aggregates,impairment of autophagy pathway,RNA processing,translation synthesis,axonal transport,endoplasmic reticulum stress,calcium channel and neuroprotection.A review for recent progress made on clinical characterization and molecular genetics of dHMN is provided.