The clinical, histological, and genotypic spectrum of SEPN1-related myopathy: A case series

Objective: To clarify the prevalence, long-term natural history and severity determinants of SEPN1-related myopathy (SEPN1-RM), we analyzed a large international case series.

Methods: Retrospective clinical, histological and genetic analysis of 132 pediatric and adult patients (2-58 years) followed-up for several decades.

Results: The clinical phenotype was marked by severe axial muscle weakness, spinal rigidity and scoliosis (86.1%, from 8.9±4 years), with relatively-preserved limb strength and previously-unreported ophthalmoparesia in severe cases. All patients developed respiratory failure (from 10.1±6 years), 81.7% requiring ventilation while ambulant. Histopathologically, 79 muscle biopsies showed large variability, partly determined by site of biopsy and age. Multi-minicores were the most common lesion (59.5%), often associated with mild dystrophic features and occasionally with eosinophilic inclusions. Identification of 65 SEPN1 mutations, including 32 novel ones and the f...

【研究目的】为明确SEPN1相关肌病（SEPN1-related myopathy, SEPN1-RM）的患病率、长期自然病程及严重程度影响因素，本研究对大型国际病例队列展开了分析。【研究方法】本研究对132例年龄介于2~58岁的儿童及成人患者开展回顾性临床、组织病理学与遗传学分析，所有患者均接受了数十年的随访。【研究结果】该疾病的临床表型以严重轴性肌无力、脊柱僵硬及脊柱侧凸为核心特征（占总病例的86.1%，发病年龄为8.9±4岁），患者肢体肌力相对保留，重症病例中可见此前未被报道的眼肌麻痹。所有患者均出现呼吸衰竭，发病年龄为10.1±6岁，其中81.7%的患者在仍能自主行走时即需要通气支持。组织病理学层面，79份肌肉活检标本可见显著异质性，该异质性部分受活检部位与患者年龄影响。多微小核心病变为最常见的病理改变（占比59.5%），常伴随轻度营养不良性病理特征，偶可见嗜酸性包涵体。本研究共鉴定出65个SEPN1基因突变，其中32个为新发突变，以及……