Gerstmann-Sträussler-Scheinker syndrome neuropathology in a Creutzfeldt-Jakob disease-like phenotype patient caused by a novel 6-OPRI sequence in the PRNP gene.

Gerstmann-Sträussler-Scheinker syndrome is an extremely rare hereditary human prion disease caused by distinct mutations in the prion protein-encoding gene and is frequently associated with a positive family history. The disease typically presents with progressive cerebellar symptoms such as gaze apraxia with limb ataxia and axial ataxia; thus, the diagnostic process is often challenging due to nonspecific clinical presentation. We present a case of a 73-year-old patient with no family history of dementia and cerebellar symptomatology during the course of rapidly progressing dementia. Owing to the clinical suspicion of prion disease, antemortem analysis of cerebrospinal fluid using a real-time quaking-induced conversion (RT-QuIC) assay was performed, with positive results. Postmortem histopathological examination confirmed a familiar form of human prion disease with concomitant asymptomatic tauopathy. An additional finding was a novel 6 octapeptide repeat insertion mutation in the prion gene. Familiar cases with an increasing number of repeated insertions seem to be associated with a longer overall disease course, milder clinical deterioration and often false-negative RT-QuIC results. The performance of RT-QuIC in inherited prion diseases may vary. Our case, involving a 6 octapeptide repeat insertion mutation, is particularly noteworthy due to the rapidly progressive clinical course and positive RT-QuIC results in both antemortem and postmortem tissue analyses.