LAMA2基因突变致先天性肌营养不良的周围神经损害研究

Peripheral nerve injury in LAMA2-related congenital muscular dystrophy patients

目的探讨LAMA2基因突变致先天性肌营养不良的周围神经损害及其性质。方法对2002至2015年在北京大学第一医院儿科就诊，经基因及分子病理检测确诊，且完成神经传导速度（NCV）和针极肌电图检查的17例LAMA2基因突变致先天性肌营养不良患儿病例资料进行回顾性总结分析，对电生理检查结果进行Pearson相关分析，并对其中1例患儿行腓肠神经活检病理研究。结果17例确诊的LAMA2基因相关肌营养不良患儿表型均为先天性肌营养不良，其中男13例、女4例，行电生理检查时年龄1月龄～6岁。肌电图提示肌源性损害17例，合并神经传导速度减慢10例，单纯肌源性损害7例。共检测周围神经95根，其中有26根神经传导速度减慢，神经传导速度较同年龄段正常平均值减慢17%～47%。正中神经、尺神经、胫神经、腓总神经的运动神经传导下降速度与病程均存在负相关（r＝－0.737、－0.771、－0.540、－0.682，P均〈0.05）。腓肠神经活检病理表现证实为髓鞘性周围神经病变。结论LAMA2基因相关肌营养不良患儿可有周围神经损害，以髓鞘病变为主，且周围神经传导速度减慢随病程延长而加重。

Objective To explore the injury pattern and features of peripheral nerve in congenital muscular dystrophy patients caused by LAMA2 gene mutation. Method Seventeen patients genetically or molecular pathologically diagnosed as LAMA2-related congenital muscular dystrophy were recruited in Peking University First Hospital between 2002 and 2015. All the patients received nerve conduction velocity （NCV） and needle electromyography tests. Clinical and laboratory examination data of the patients was retrospectively analyzed. The correlation between the NCV and disease course was determined by Pearson correlation analysis. Additionally, one patient underwent a sural nerve biopsy. Result Among these 17 identified patients （13 male and 4 female） , all of them were diagnosed as congenital muscular dystrophy, and all of them underwent electrophysiologieal examination at ages between 1 month to 6 years. Electromyogram indicated seventeen patients of myogenic damage, of whom 10 cases were complicated with reduced NCV. Twenty-six of 95 analyzed nerves showed NCV slower than the normal average of contemporary in 17% -47%. Correlation analysis between NCV and the disease course indicated that NCV of median nerves, ulnar nerves, tibial nerves and common peroneal nerves were negatively associated with the disease course （r = - 0. 737, - 0. 771, - 0. 540 and - 0. 682, respectively; all P 〈 0. 05 ）. Sural nerve biopsy revealed peripheral neuropathy changes of myelin. Conclusion There is peripheral nerve injury in LAMA2- related muscular dystrophy patients. It mainly manifests as demyelinating lesions. Moreover, the NCV of peripheral nerve will decrease with the increase of the course of the disease.