Ma Jing, Zhang Huiqiu, Meng Bing, Qin Jiangbo, Liu Hongye, Pang Xiaomin, Zhao Rongjuan, Wang Juan, Chang Xueli, Guo Junhong, Zhang Wei
Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, China.
Department of Neurology, First Clinical Medical College, Shanxi Medical University, Taiyuan, China.
J Clin Neurol. 2024 Nov;20(6):580-590. doi: 10.3988/jcn.2023.0486.
CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene () has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature.
The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of was tested using the repeat-primed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats.
Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in as the causative mutation in the two patients.
Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.
Notch 2 N端样C基因（）5'非翻译区（5'UTR）中的CGG重复扩增与神经元核内包涵体病（NIID）和3型眼咽远端肌病（OPDM3）相关。报道的OPDM3患者较少。本报告描述了两名具有新影像学表现的OPDM3患者，他们呈现出NIID的典型特征，并回顾了文献中所有可用的OPDM3病例。
回顾并研究了可用的临床、影像学和病理学信息。使用重复引物聚合酶链反应（PCR）检测中5'UTR的CGG重复扩增，随后进行荧光扩增子长度PCR以确定CGG重复的数量。
我们的两名OPDM3患者以及文献中报道的大多数患者都出现了NIID的典型临床特征，包括白质脑病、周围神经病变、认知衰退、色素性视网膜病变、共济失调、震颤、急性脑炎样发作、色素性视网膜病变、瞳孔缩小和感音神经性听力损失。除了NIID的典型影像学表现外，我们的两名患者在小脑中脚出现了扩散加权成像（DWI）高信号，这在以前尚未有过描述。肌肉活检显示两名患者的肌纤维中均有边缘空泡和p62阳性核内包涵体。对一名患者进行的皮肤活检检测到典型嗜酸性核内包涵体。基因分析确定中CGG重复扩增是这两名患者的致病突变。
我们的两名OPDM3患者具有NIID的临床特征，并在小脑中表现出DWI异常。我们的结果表明，OPDM3属于NIID范畴，小脑中的DWI高信号有助于诊断NIID或OPDM3。
