Clinical, pathological and gene variation characteristics of 16 patients with chronic progressive external ophthalmoplegia / 中华神经医学杂志

ABSTRACT

Objective:To investigate the clinical characteristics, skeletal muscle pathologies and gene variations of chronic progressive external ophthalmoplegia (CPEO).Methods:Sixteen patients with conformed CPEO, admitted to our hospital from January 1997 to December 2021, were chosen. Their clinical data such as onset age and course of diseases and muscle pathological examination results were collected and their gene variation characteristics were analyzed.Results:The initial symptom in all 16 patients was ptosis of varying degrees; 15 patients were with eye movement disorder, 6 with diplopia, 4 with proximal limb weakness, and 3 with dysphagia and dysarthria. Among the 16 patients, electromyography showed myogenic damage in 7 patients, myogenic combined with neurogenic damage in 1 patient, neurogenic damage in 1 patient, and normal in 7 patients. Skeletal muscle biopsies indicated that 14 patients were with ragged red fibers (RRF), 11 patients had cytochrome C oxidase (COX)-negative muscle fibers, 3 patients had a small amount of degenerated and necrotic myofibers with mononuclear phagocytic infiltration. Immunohistochemical staining indicated infiltration of CD8 and CD68 positive lymphocytes. Ten patients accepted genetic test, indicating 6 patients with single large fragment deletion of mitochondrial DNA (mtDNA), 1 patient with mtDNA point mutation, 1 patient with nucleosomal DNA (nDNA) point mutation, and 2 patients without pathogenicity variation clearly associated with clinical phenotype. Electron microscopy in 5 patients showed that abnormal mitochondrial aggregation was noted in 4 patients under the sarcolemma and among the myofibrils.Conclusion:In addition to ptosis and eye movement disorders, a small number of patients with CPEO may be accompanied by dysphagia and limb weakness; and single large fragment deletion of mtDNA is the main mutation form of CPEO.