Gerstmann‐Sträussler‐Scheinker Disease Presenting as Late‐Onset Slowly Progressive Spinocerebellar Ataxia, and Comparative Case Series with Neuropathology.

Background: Genetic prion diseases, including Gerstmann‐Sträussler‐Scheinker disease (GSS), are extremely rare, fatal neurodegenerative disorders, often associated with progressive ataxia and cognitive/neuropsychiatric symptoms. GSS typically presents as a rapidly progressive cerebellar ataxia, associated with cognitive decline. Late‐onset cases are rare. Objective: To compare a novel GSS phenotype with six other cases and present pathological findings from a single case. Methods: Case series of seven GSS patients, one proceeding to autopsy. Results: Case 1 developed slowly progressive gait difficulties at age 71, mimicking a spinocerebellar ataxia, with a family history of balance problems in old age. Genome sequencing revealed a heterozygous c.392G > A (p.G131E) pathogenic variant and a c.395A > G resulting in p.129 M/V polymorphism in the PRNP gene. Probability analyses considering family history, phenotype, and a similar previously reported point mutation (p.G131V) suggest p.G131E as a new pathogenic variant. Clinical features and imaging of this case are compared with those six additional cases harboring p.P102L mutations. Autopsy findings of a case are described and were consistent with the prion pathology of GSS. Conclusions: We describe a patient with GSS with a novel p.G131E mutation in the PRNP gene, presenting with a late‐onset, slowly progressive phenotype, mimicking a spinocerebellar ataxia, and six additional cases with the typical P102L mutation. [ABSTRACT FROM AUTHOR]