Abstract
BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by a wide range of clinical manifestations. GGC-repeat expansion in NOTCH2NLC was recently identified as the genetic cause of NIID. Here we report clinical, radiological, pathological, and genetic findings in NIID patients. METHODS: Twenty-five NIID patients from 22 unrelated families of Korean ancestry were reviewed from 9 referral centers in South Korea. We compared clinical features between sporadic and familial NIID patients. We classified NIID patients according to their prominent symptoms. The presence of GGC repeat expansion was analyzed in 19 patients. RESULTS: The 25 reviewed NIID patients comprised 12 (48.0%) sporadic and 13 (52.0%) familial cases, with the latter showing a significantly higher proportion of males (p=0.027). The patients were classified into three subtypes based on the prominent symptoms: NIID-Episodic (44.0%), NIID-EPS (extrapyramidal symptoms) (36.0%), and NIID-Dementia (20.0%). Most patients (92.0%) also exhibited other symptoms, including peripheral neuropathy (60.0%), bladder dysfunction (48.0%), or ophthalmic problems (56.0%). Hyperintensities along the corticomedullary junctions in diffusion-weighted imaging and extensive white-matter hyperintensities in fluid-attenuated inversion-recovery imaging were observed in 96.0% and 100% of the patients, respectively. GGC repeat expansion in NOTCH2NLC was identified in 6 sporadic and 10 familial cases. The number of GGC repeats was not correlated with the onset age or clinical symptoms. CONCLUSIONS: This study has highlighted the diverse phenotypes and genetic profiles of Korean NIID patients, and provided valuable insights into this rare disorder.