Oculomotor dysfunction with unremarkable neuroimaging: a diagnostic clue to Gerstmann-Sträussler-Scheinker syndrome.

BACKGROUND

Gerstmann-Sträussler-Scheinker syndrome (GSS) is an extremely rare genetic prion disease caused by pathogenic mutations in the prion protein gene (PRNP). Further reports and thorough evaluation are needed to identify and manage this disease.

METHOD: We report a rare case of GSS in a 56-year-old woman who presented with progressive gait instability, dizziness, and speech difficulties.

RESULTS

Initial genetic screening for 12 common spinocerebellar ataxia (SCA) subtypes via PCR-based fragment analysis was negative. However, detailed video-oculography (VOG) revealed key ocular motor abnormalities, including spontaneous upbeat nystagmus with a decreasing slow phase velocity, macro-square wave jerks, horizontal gaze-evoked nystagmus, saccadic hypermetria, and decreased optokinetic nystagmus. Given the family history of gait instability and these specific findings, whole-exome sequencing (WES) was performed, which identified a heterozygous p.Pro102Leu (P102L) mutation in the PRNP gene. Neuroimaging was unremarkable, highlighting the clinical-radiological dissociation.

CONCLUSIONS

This case demonstrates that a distinctive oculomotor signature can serve as a critical phenotypic lead for GSS, particularly justifying expanded genetic evaluation when conventional SCA panels and neuroimaging are non-diagnostic.