遗传性压迫易感性神经病的临床、电生理、病理和基因突变分析

目的:观察遗传性压迫易感性神经病(hereditary neuropathy with liability to pressure palsies,HNPP)的临床、电生理、病理及遗传学特点,以提高对本病的认识及诊断水平。方法:对5例HNPP患者进行详尽的临床检查、神经电生理、腓肠神经活检,用多聚酶链反应(PCR)结合酶切方法检测HNPP患者17p11.2的基因缺失。结果:本组有3例来自同一家系,符合常染色体显性遗传模式,另2例为散发。多在20岁前起病,表现为复发性、无痛性、局灶性单神经病或多神经病,多于数天或数月内自行恢复,少数可遗留部分神经功能缺损。神经电生理检查有广泛性运动和感觉神经传导速度减慢,于易嵌压部位传导速度减慢更明显,并有远端运动潜伏期延迟。腓肠神经活检显示部分有髓神经纤维明显增粗,电镜可见有髓纤维髓鞘增厚,髓鞘板层层数增加。基因检测发现有3例存在17p11.2区包含PMP22基因在内的1.5Mb片段的缺失突变。结论:HNPP是一种常染色体显性遗传病,但也有散发,多于儿童期或青少年起病,表现为外伤或受压后反复出现肢体麻木、无力;生理的特点为广泛性神经传导速度减慢及远端运动潜伏期延迟;肌电图是诊断HNPP的重要筛选方法,有利于发现更多的病例;病理学特征是髓鞘增粗或典型的腊肠样结构;7p11.2区包含PMP22基因在内的1.5Mb片段的缺失突变是HNPP国人最常见的基因型,重组热点多位于REP的3.2kb区域内。

Clinical, electrophysiological, pathological and genomic study of hereditary neuropathy with liability to pressure palsies

Objective：To explore the clinical,electrophysiological,pathological and genomic features of HNPP and promote the understanding and diagnostic acuity of the disease.Methods：5 cases of HNPP underwent detailed clinical examinations,electromyogram,sural nerve biopsies.Polymerase chain reaction（PCR）combined with restricion enzyme digestion were used to detect gene deletion on chromosome 17p11.2.Results：3 patients came from one family and it was consistent with autosomal dominant inheritance.Age at onset was in the first or second decade.The clinical features were weakness,numbness as recurrent mononeuropathy precipitated by trivial traumas.Symptoms often disappeared spontaneously after a few days or a few months.Electrophysiological study demonstrated diffused peripheral nerve damage with decreased nerve condution velocity especially at common entrapment sites and delayed distal motor latency.The nerve biopsy showed the presence of some large thickened myelinated fibers.Gene mutation analysis showed that 3 cases have large fragment tandem deletions containing peripheral myelinprotein 22（PMP22）.Conclusions：Although HNPP is concerned with heredity,We also find two sporadic cases.It usually begins in childhood or adolescence,characterized by recurrent weakness and numbness of limbs precipitated by compression.Electrophysiological studies show generalized neuropathy with decreased conduction velocities and delayed distal motor latency.Electrophysiologic examination is an important screen method.The histopathological feature has been found to be ＂sausage-like＂ tomaculous changes of myelin sheath.A 1.5-megabase deletion on chromosome 17p11.2,encompassing the PMP22 gene is the main mutation type of HNPP.