First case of adult onset neuronal intranuclear inclusion disease with both typical radiological signs and NOTCH2NLC repeat expansions in a Caucasian individual

Abstract Background and purpose Adult onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with a heterogeneous clinical presentation that can mimic stroke and various forms of dementia. To date, it has been described almost exclusively in Asian individuals. Methods This case presentation includes magnetic resonance imaging (MRI) of the neurocranium, histology by skin biopsy, and long‐read genome sequencing. Results A 75‐year‐old Caucasian female presented with paroxysmal encephalopathy twice within a 14‐month period. Brain MRI revealed high‐intensity signals at the cerebral corticomedullary junction (diffusion‐weighted imaging) and the paravermal area (fluid‐attenuated inversion recovery), a typical distribution observed in adult onset NIID. The diagnosis was corroborated by skin biopsy, which demonstrated eosinophilic intranuclear inclusion bodies, and confirmed by long‐read genome sequencing, showing an expansion of the GGC repeat in exon 1 of NOTCH2NLC . Conclusions Our case proves adult onset NOTCH2NLC ‐GGC‐positive NIID with typical findings on MRI and histology in a Caucasian patient and underscores the need to consider this diagnosis in non‐Asian individuals.