Objective: Describe an atypical presentation of Gerstmann-Sträussler-Scheinker disease (GSS) with predominant parkinsonism due to the PRNP P102L mutation, emphasizing intrafamilial variability and diagnostic challenges in Colombia.

Background: GSS, a rare autosomal dominant prion disease caused by PRNP mutations, typically presents with cerebellar ataxia and dementia. The P102L variant is classically linked to ataxia, but this case highlights parkinsonism as the initial manifestation, a rare phenotype. Underreporting in Colombia obscures disease incidence and clinical diversity.

Method: A 55-year-old Colombian woman with progressive parkinsonism, dysphagia, and cognitive decline underwent neurologic evaluation, brain MRI, electromyography, and whole-genome sequencing. Familial genetic testing and counseling were conducted.

Results: Clinical evaluation revealed rigidity, bradykinesia, resting tremor, and rapid functional decline. MRI showed nonspecific white matter hyperintensities without cerebellar atrophy. Genetic testing confirmed the heterozygous PRNP P102L mutation. Thirteen family members were diagnosed, four confirmed genetically, with similar parkinsonian onset. Levodopa provided partial symptom relief. The patient died within two years from pneumonia.

Conclusion: This case underscores GSS’s phenotypic variability, even with the P102L mutation, and challenges the classic ataxia-dominant presentation. Parkinsonism as an initial feature necessitates prion disease inclusion in atypical parkinsonism differentials. Genetic testing enables early diagnosis, family counseling, and palliative planning. Colombian underreporting highlights the need for improved surveillance.

Figure 1. Family pedigree

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