Clinical features ofNOTCH2NLC-related neuronal intranuclear inclusion disease
Open Access
- 23 September 2022
- journal article
- research article
- Published by BMJ in Journal of Neurology, Neurosurgery & Psychiatry
- Vol. 93 (12), 1289-1298
- https://doi.org/10.1136/jnnp-2022-329772
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, pConclusions 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.Keywords
Funding Information
- Natural Science Foundation of Hunan Province (2020JJ5923)
- National Natural Science Foundation of China (81971029)
- National Key R&D Program of China (2020YFC2008500, 2022ZD0213700)
- Hunan Innovative Province Construction Project (2019SK2335)
- National Major Projects in Brain Science and Brain-like Research (2021ZD0201803)
This publication has 41 references indexed in Scilit:
- MR Imaging Features of the Cerebellum in Adult-Onset Neuronal Intranuclear Inclusion Disease: 8 CasesAmerican Journal of Neuroradiology, 2017
- Neuronal intranuclear (hyaline) inclusion disease and fragile X-associated tremor/ataxia syndrome: a morphological and molecular dilemmaBrain, 2017
- Over 10 years MRI observation of a patient with neuronal intranuclear inclusion diseaseBMJ Case Reports, 2017
- Clinicopathological features of adult-onset neuronal intranuclear inclusion diseaseBrain, 2016
- Memory Loss and Frontal Cognitive Dysfunction in a Patient with Adult-onset Neuronal Intranuclear Inclusion DiseaseInternal Medicine, 2016
- Neuronal intranuclear inclusion disease cases with leukoencephalopathy diagnosed via skin biopsyJournal of Neurology, Neurosurgery & Psychiatry, 2013
- The Unstable Repeats—Three Evolving Faces of Neurological DiseaseNeuron, 2013
- Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathyNeurology, 2005
- Neuronal intranuclear hyaline inclusion diseaseNeuropathology, 2003
- Unstable trinucleotide repeats and the diagnosis of neurodegenerative diseaseHuman Pathology, 1994