Sporadic late-onset nemaline myopathy (SLONM) is an enigmatic, supposedly very rare, putatively immune-mediated late-onset myopathy, typically presenting with subacutely progressive limb-girdle muscular weakness, yet slowly progressing cases have been described too. We systematically studied (para)clinical and histopathological findings in a cohort of 18 isolated yet suspected inherited myopathy patients, showing late-onset, slowly progressive limb-girdle muscle weakness, remaining unsolved after whole-exome sequencing. The presence of a monoclonal gammopathy of unknown significance (MGUS) and anti-HMGCR antibodies was determined. Biopsies were systematically re-evaluated and systematic immunohistochemical and electron microscopy studies were performed to particularly evaluate the presence of rods and/or inflammatory features. Ten patients showed rods as core feature on muscle biopsy on re-evaluation, four of these had an IgG κ MGUS in blood. As such, these ten patients represented suspected slowly progressing SLONM patients, with auxiliary data supporting this diagnosis: 1) additional muscle biopsy features pointing towards Z-disk and myofibrillar pathology; 2) a common selective pattern of muscle involvement on MRI; 3) inflammatory features on muscle biopsy. Findings in this proof-of-concept study highlight difficulties in reliably diagnosing slowly progressing SLONM and the probably underestimated prevalence of this entity in cohorts of whole exome sequencing negative myopathy patients, initially considered having an inherited myopathy.

散发性迟发性线虫肌病 (SLONM) 是一种神秘的、据称非常罕见的、推定免疫介导的迟发性肌病，通常表现为亚急性进行性肢带肌无力，但也有缓慢进展的病例被描述。我们系统地研究了 18 名孤立但疑似遗传性肌病患者的（准）临床和组织病理学发现，这些患者表现出迟发性、缓慢进展的肢带肌无力，在全外显子组测序后仍未解决。确定存在意义不明的单克隆丙种球蛋白病 (MGUS) 和抗 HMGCR 抗体。系统地重新评估活检并进行系统的免疫组织化学和电子显微镜研究，以特别评估棒和/或炎症特征的存在。10 名患者在重新评估时在肌肉活检中显示棒作为核心特征，其中 4 名在血液中有 IgG κ MGUS。因此，这 10 名患者代表疑似进展缓慢的 SLONM 患者，辅助数据支持这一诊断：1）额外的肌肉活检特征指向 Z 盘和肌原纤维病理学；2) MRI 上常见的选择性肌肉受累模式；3)肌肉活检的炎症特征。这项概念验证研究的结果突出了可靠诊断缓慢进展的 SLONM 的困难，以及该实体在最初被认为患有遗传性肌病的全外显子组测序阴性肌病患者队列中可能被低估的患病率。这 10 名患者代表疑似缓慢进展的 SLONM 患者，辅助数据支持该诊断：1）额外的肌肉活检特征指向 Z 盘和肌原纤维病理学；2) MRI 上常见的选择性肌肉受累模式；3)肌肉活检的炎症特征。这项概念验证研究的结果突出了可靠诊断缓慢进展的 SLONM 的困难，以及该实体在最初被认为患有遗传性肌病的全外显子组测序阴性肌病患者队列中可能被低估的患病率。这 10 名患者代表疑似缓慢进展的 SLONM 患者，辅助数据支持该诊断：1）额外的肌肉活检特征指向 Z 盘和肌原纤维病理学；2) MRI 上常见的选择性肌肉受累模式；3)肌肉活检的炎症特征。这项概念验证研究的结果突出了可靠诊断缓慢进展的 SLONM 的困难，以及该实体在最初被认为患有遗传性肌病的全外显子组测序阴性肌病患者队列中可能被低估的患病率。3)肌肉活检的炎症特征。这项概念验证研究的结果突出了可靠诊断缓慢进展的 SLONM 的困难，以及该实体在最初被认为患有遗传性肌病的全外显子组测序阴性肌病患者队列中可能被低估的患病率。3)肌肉活检的炎症特征。这项概念验证研究的结果突出了可靠诊断缓慢进展的 SLONM 的困难，以及该实体在最初被认为患有遗传性肌病的全外显子组测序阴性肌病患者队列中可能被低估的患病率。