眼面咽喉肌受累的一个家系临床及其相关基因的初步研究

Preliminary clinical and genetic study of a family with ophthalmoplegia,dysphagia and facial weakness

目的分析呈常染色体显性遗传,核心症状为眼外肌、面肌、咽喉肌肉瘫痪的一个家系,探讨其分类和病因。方法调查包括先证者在内的5例患者以及该家系中另外26名成员,收集其临床资料,进行电生理、肌肉病理检查,收集血样用 PCR 法进行基因验证。结果 5例接受调查的患者经查体发现:眼睑下垂(5/5),眼外肌麻痹(5/5),面瘫(5/5),吞咽困难、声音嘶哑、咽反射迟钝(5/5),舌肌萎缩(3/5),颞肌萎缩(4/5),咬肌萎缩(4/5),近端肢体无力(3/5),肢体近端肌肉萎缩(4/5),远端肢体无力(3/5),肢体远端肌肉萎缩(4/5)。与眼咽型肌营养不良(OPMD)等疾病进行比较,电生理上确定病灶的性质为肌源性损害,肌肉病理为肌肉萎缩,但没有代谢性病变的表现,因此从电生理和肌肉病理两方支持肌营养不良的诊断。患者和表现健康的成员的 PABPN1基因不存在(GCG)_6(GCA)_3GCG 的突变。结论该家系临床表现类似 OPMD 而不同于其他已知疾病,但是基因背景又完全不同于 OPMD,可能属于肌营养不良的一种新亚型。

Objective To investigate the features of familiar facial palsy, ophthalmoplegia and dysphagia characterized by autosomal dominant inheritance in a family and to discuss the classification and pathogenesis of the disease. Methods Clinical, electrophysiological, pathological examinations were performed and blood samples were obtained from 5 patients and 26 family members. PCR protocol was used to identify a certain gene. Results In the 5 patients receiving physical examination, all had ptosis, external ophthalmoplegia, facial paralysis, dyphagia, hoarseness, decreased pharyngeal reflex; 4 had amyotrophy of muscle of tongue, temporal nuscle, masseter and muscles of distal lower limbs; 3 had proximal limb asthenia and distal limbs amyotrophy. Compared to those of oculopharyngeal muscular dystrophy （OPMD） with similar symptoms and signs, both electrophysiological manifestation and pathological findings of the family members supported the diagnosis of muscular dystrophy, but the （GCG） 6 （GCA） 3 GCG in the first exon of PABPN1 mutated neither in normal family members nor in patients. Conclusions This family presents clinical manifestations somewhat resembling to those of OPMD and distinctive to other disorders, but has a totally different genetic background from OPMD. It may be a new subtype of muscular dystrophy.