Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease. Issue 12 (23rd September 2022)

• Record Type: Journal Article
• Authors: Tian, Yun; Zhou, Lu; Gao, Jing; Jiao, Bin; Zhang, Sizhe; Xiao, Qiao; Xue, Jin; Wang, Ying; liang, Hui; Liu, Yaling; Ji, Guang; Mao, Chenhui; Liu, Caiyan; Dong, Liling; Zhang, Long; Zhang, Shugang; Yi, Jiping; Zhao, Guohua; Luo, Yingying; Sun, Qiying; Zhou, Yafang; Yi, Fang; Chen, Xiaoyu; Zhou, Chaojun; Xie, Nina; Luo, Mengchuan; Yao, Lingyan; Hu, Yacen; Zhang, Mengqi; Zeng, Qiuming; Fang, Liangjuan; Long, Hong-Yu; Xie, Yuanyuan; Weng, Ling; Chen, Si; Du, Juan; Xu, Qian; Feng, Li; Huang, Qing; Hou, Xuan; Wang, Junpu; Xie, Bin; Zhou, Lin; Long, Lili; Guo, Ji-feng; Wang, Junling; Yan, Xinxiang; Jiang, Hong; Xu, Hongwei; Duan, Ranhui; Tang, Beisha; Shen, Lu;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93:Issue 12(2022)
• Page Start: 1289
• Page End: 1298
• Publication Date: 2022-09-23
• Subjects: clinical neurology -- neurogenetics; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-329772
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Abnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC -related NIID in China. Methods: Patients with NOTCH2NLC -related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy. Results: In the 247 patients with NOTCH2NLC -related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=−0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission. Conclusions: NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC -related NIID.