Neuronal intranuclear inclusion disease is genetically heterogeneous.
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ABSTRACT:
SUBMITTER: Chen Z
PROVIDER: S-EPMC7480908 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Neuronal intranuclear inclusion disease is genetically heterogeneous.
Chen Zhongbo Z Yan Yau Wai W Jaunmuktane Zane Z Tucci Arianna A Sivakumar Prasanth P Gagliano Taliun Sarah A SA Turner Chris C Efthymiou Stephanie S Ibáñez Kristina K Sullivan Roisin R Bibi Farah F Athanasiou-Fragkouli Alkyoni A Bourinaris Thomas T Zhang David D Revesz Tamas T Lashley Tammaryn T DeTure Michael M Dickson Dennis W DW Josephs Keith A KA Gelpi Ellen E Kovacs Gabor G GG Halliday Glenda G Rowe Dominic B DB Blair Ian I Tienari Pentti J PJ Suomalainen Anu A Fox Nick C NC Wood Nicholas W NW Lees Andrew J AJ Haltia Matti J MJ Hardy John J Ryten Mina M Vandrovcova Jana J Houlden Henry H
Annals of clinical and translational neurology 20200810 9
Neuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases of neurodegenerative disease with intranuclear inclusions and applied in silico-based screening using whole-genome sequencing data from 20 536 partic ...[more]
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Project description:Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with various neurological manifestations, including tremor. Here, we report a case involving a 68-year-old man with an 8-year history of tremor in his right arm. Subsequently, examination revealed that the patient was suffering from a low-frequency, high-amplitude, and posture-induced proximal arm tremor elicited by sustained arm abduction with flexed elbows (wing-beating tremor), which was partially improved by zonisamide treatment. Abnormal expansion of GGC repeats in the NOTCH2NLC gene confirmed the diagnosis of NIID. This case highlights the fact that unilateral wing-beating tremor can be a manifestation of NIID. Zonisamide may be effective for controlling tremors associated with NIID.
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Project description:Background: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Because of variable clinical manifestations, NIID was often misdiagnosed. According to published case reports, the common clinical manifestations of NIID include dementia, muscle weakness, autonomic impairment, sensory disturbance, rigidity, ataxia convulsions, etc. However, no cases of oromandibular dystonia were mentioned. Case Presentation: We describe a case of a 58-year-old woman presenting with mouth involuntary chewing initially. She started to show hand tremors, ataxia, and walking instability until 2 years later. Diffusion-weighted imaging showed high intensity signal along the corticomedullary junction. Fluid-attenuated inversion recovery imaging showed white matter hyperintensity. Electromyography (EMG) indicated peripheral nerve degeneration. Neuropsychological testing showed memory loss. Finally, skin biopsy and GGC repeat expansions in the NOTCH2NLC (Notch 2 N-terminal like C) gene confirmed the diagnosis of NIID. Conclusion: This case demonstrated that oromandibular dystonia could be the first symptom of NIID. This case report provides new characteristics of NIID and broadens its clinical spectrum.
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Project description:Neuronal intranuclear inclusion disease is a rare, neurodegenerative disorder with onset in childhood. We report a single case natural history over 10 years and present a review of juvenile parkinsonism and neuronal intranuclear inclusion disease. Our patient was initially seen at the University of Rochester at age 12 years after 4 years of progressive dysarthria, dysphagia, and clumsiness. His neurologic examination was notable for parkinsonism. He had excellent initial response to levodopa, but subsequently developed dopa-induced motor fluctuations, dyskinesias, psychosis, and dystonia. Later in the course, he developed multiple nonmotor symptoms and ultimately died from respiratory failure. Neuropathology demonstrated large eosinophilic nuclear inclusions and small ubiquitin-related modifier 1 (SUMO-1) immunoreactivity, confirming the diagnosis of neuronal intranuclear inclusion disease. This diagnosis should be considered in a patient presenting with juvenile parkinsonism. Clues to the diagnosis include early-onset dopa-induced dyskinesias, gastrointestinal dysfunction, and oculogyric crises.
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Project description:Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by the presence of eosinophilic hyaline intranuclear inclusions. Owing to its widely varying clinical manifestations, NIID is frequently misdiagnosed or overlooked. However, a characteristic high-intensity corticomedullary junction signal on diffusion-weighted imaging (DWI) is often indicative of NIID. In this study, we described the case of two sisters with NIID who presented with distinct symptoms and imaging data. The younger sister showed symptoms similar to those of mitochondrial encephalopathy, with a reversible high-intensity signal from the cortex on T2 and DWI. The elder sister showed a characteristic high-signal "ribbon sign" in the corticomedullary junction on DWI. Skin biopsy confirmed that both had neuronal intranuclear inclusion. Two years later, the younger sister also developed the characteristic high-signal "ribbon sign" in the corticomedullary junction on DWI. This case study provides new insights into the complexity of NIID. The findings suggest that patients with this condition, including those belonging to the same family, may exhibit varying clinical and imaging features at different times.
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