• Yun Tian, Lu Zhou, Jing Gao, Bin Jiao, Sizhe Zhang, Qiao Xiao, Jin Xue, Ying Wang, Hui Liang, Yaling Liu, Guang Ji, Chenhui Mao, Caiyan Liu, Liling Dong, Long Zhang, Shugang Zhang, Jiping Yi, Guohua Zhao, Yingying Luo, Qiying Sun, Yafang Zhou, Fang Yi, Xiaoyu Chen, Chaojun Zhou, Nina Xie, Mengchuan Luo, Lingyan Yao, Yacen Hu, Mengqi Zhang, Qiuming Zeng, Liangjuan Fang, Hong-Yu Long, Yuanyuan Xie, Ling Weng, Si Chen, Juan Du, Qian Xu, Li Feng, Qing Huang, Xuan Hou, Junpu Wang, Bin Xie, Lin Zhou, Lili Long, Ji-Feng Guo, Junling Wang, Xinxiang Yan, Hong Jiang, Hongwei Xu, Ranhui Duan, Beisha Tang, and Lu Shen.
• Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
• J. Neurol. Neurosurg. Psychiatr. 2022 Dec 1; 93 (12): 128912981289-1298.

BackgroundAbnormal 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.MethodsPatients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy.ResultsIn 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.ConclusionsNIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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