全新单一大片段线粒体DNA缺失的慢性进行性眼外肌麻痹1例

A case of chronic progressive external ophthalmoplegia with a novel large-scale deletion

44岁女性,进行性外斜视和垂直斜视15年。眼部检查:双眼前节和眼底未见明显异常。屈光检查:双眼中度近视,矫正视力5.0。斜视专科检查如下。右眼上睑轻度下垂,外斜视合并垂直斜视。眼球运动:右眼内转、上转受限,左眼内转、上转、下转受限。全身检查:颅脑磁共振成像(MRI)回报斜坡信号欠均匀,未见强化;蝶窦异常信号,考虑炎症可能。眼眶MRI见眼外肌萎缩变细。重症肌无力相关检测指标阴性。外周血panel检测,发现线粒体基因组的chrM-11084有单个碱基突变。对眼外肌组织进行线粒体DNA检测,发现m.6469-15590存在约9122 bp缺失。外周血以及组织电泳结果与测序一致。患者经斜视手术治疗,眼位明显改善,双眼视功能部分恢复。讨论体会:慢性进行性眼外肌麻痹临床表现易误诊为眼肌型重症肌无力。诊断依靠病史、临床表现以及影像学检查。线粒体疾病DNA缺失具有组织异质性的特点,肌肉组织活检和基因检测是诊断的金标准。

A 44-year-old female patient presented with progressive exotropia and vertical strabismus for 15 years.Eye examinations were unremarkable in the anterior segment and fundus of both eyes.Refractive examination showed moderate myopia in both eyes,with a corrected vision of 20/20.Special examination of strabismus:the upper eyelid of the right eye was slightly drooping,exotropia was combined with vertical strabismus,and the eye movement was limited in both eyes.Magnetic resonance imaging(MRI)reported that the signal of clivus was not uniform,without enhancement;Abnormal signal was observed in the sphenoid sinus,which was considered as a possibility of inflammation.Orbital MRI showed atrophy and thinning of extraocular muscles.The relevant indicators of myasthenia gravis were negative.Peripheral blood panel detection showed that there was a single base mutation in the chrM-11084 of mitochondrial genome.Mitochondrial DNA detection of extraocular muscle tissue showed that there was about a 9122 bp-deletion in the m.6469-15590.The results of peripheral blood and tissue electrophoresis were consistent with the sequencing.After strabismus surgery,the eye position of the patient was significantly improved,and the binocular visual function was partially restored.The clinical manifestation of chronic progressive extraocular muscle paralysis is easily misdiagnosed as ophthalmic myasthenia gravis.Diagnosis depends on medical history,clinical manifestation and imaging examination.DNA deletion in mitochondrial diseases is characterized by tissue heterogeneity.Muscle biopsy and gene detection are the gold standard for diagnosis.