Familial adult-onset neuronal intranuclear inclusion disease: A case report and literature review.

Abstract

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with highly variable clinical manifestations, making diagnosis challenging. Recent advancements in genetic and pathological testing, such as the identification of GGC repeat expansions in the NOTCH2NLC gene, have improved diagnostic accuracy, but familial cases remain underreported. This report details 3 cases of familial adult-onset NIID in 2 sisters and 1 brother. The older sister experienced episodic encephalopathy and autonomic dysfunction for over 40 years, while the younger sister presented similar symptoms 5 years ago. The brother also developed episodic encephalopathy 5 years ago. Brain diffusion-weighted imaging (DWI) for all 3 patients revealed hyperintensity at the corticomedullary junction and corpus callosum. Skin biopsies from the older sister and brother confirmed the presence of p62 antibody-positive intranuclear inclusion bodies in sweat gland cells and fibroblasts. Genetic testing showed 146 and 133 GGC repeats in the NOTCH2NLC gene in the older sister and brother, respectively. All 3 patients were diagnosed with NIID based on clinical, radiological, and genetic findings. The patients received hormonal therapy, circulation-enhancing treatments, and rehydration therapy during acute episodes. All 3 patients showed significant improvement in symptoms following treatment, with a return to baseline function after hospital discharge. Proper management of NIID includes prompt recognition of symptoms, adequate rest, and avoidance of triggers such as fatigue, infections, and stress, which may reduce the frequency of episodic attacks. Early diagnosis and targeted symptomatic treatment are essential for improving patient outcomes.