In:
Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 93, No. 12 ( 2022-12), p. 1289-1298
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-3050
,
1468-330X
DOI:
10.1136/jnnp-2022-329772
Language:
English
Publisher:
BMJ
Publication Date:
2022
detail.hit.zdb_id:
1480429-3
