Journal Article

Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease

Huang, Qing, Yan, Xinxiang, Xie, Nina, Jiao, Bin, Zhao, Guohua, Xie, Yuanyuan, Wang, Ying, Zhang, Shugang, Hu, Yacen, Luo, Mengchuan, Zhang, Mengqi, Guo, Ji-feng, Zhang, Sizhe, Yi, Jiping, Liu, Yaling, Weng, Ling, Wang, Junling, Xu, Qian, Zhou, Chaojun, Chen, Si, Mao, Chenhui, Hou, Xuan, Luo, Yingying, Long, Lili, Feng, Li, Wang, Junpu, Ji, Guang, Zhou, Lin, Du, Juan, Dong, Liling, liang, Hui, Tian, Yun, Yao, Lingyan, Yi, Fang, Xu, Hongwei, Fang, Liangjuan, Duan, Ranhui, Zeng, Qiuming, Xie, Bin, Zhang, Long, Zhou, Yafang, Gao, Jing, Chen, Xiaoyu, Liu, Caiyan, Tang, Beisha, Xue, Jin, Jiang, Hong, Xiao, Qiao, Zhou, Lu, Sun, Qiying, Long, Hong-Yu, Shen, Lu

2022

Overview

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.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Alzheimer's disease / Biopsy / clinical neurology / Cognitive ability / Cross-Sectional Studies / Dementia / Dementia - pathology / Genetic testing / Genotype & phenotype / Humans / Intranuclear Inclusion Bodies - genetics / Intranuclear Inclusion Bodies - pathology / Movement Disorders / Muscle Weakness - pathology / Neurogenetics / Peripheral Nervous System Diseases - pathology / Peripheral neuropathy / Variables