Objective: The objective of this report is to describe previously unreported features in a patient with Gerstmann-Straussler-Scheinker syndrome (GSS) due to the F198S mutation.

Background: GSS is an autosomal dominant prion disease caused by point mutations in the PRNP gene. Among reported genotypes, shared features include cerebellar ataxia, parkinsonism, cognitive decline, and psychiatric disease(1). Two cases of GSS due to the D202N mutation describe parkinsonism and abnormal DaT-SPECT imaging, with one reporting motor benefit with levodopa (2,3). A case of dopaminergic nonresponsive parkinsonism with abnormal DaT-SPECT imaging was reported with the A117V mutation (4). Original reporting of the Indiana kindred establishing linkage to the F198S mutation noted dopamine-responsive extrapyramidal signs, but did not comment on treatment-related dyskinesia, and DaT-SPECT was unavailable (5).

Method: A 71 year old man developed forgetfulness in his 60s. At age 66 he developed progressive expressive language deficits with effortful speech, followed by ataxia and akinetic-rigid parkinsonism. He was started on levodopa without effect initially. Upon evaluation at our center after relocating, his examination disclosed a supranuclear gaze palsy, generalized chorea of the face, trunk and limbs, multifocal myoclonus, asymmetric irregular jerky rest tremor, bilateral bradykinesia and rigidity, and ataxic gait. Levodopa was discontinued. On followup chorea was absent, bradykinesia and rigidity were worse, and he could not stand, but myoclonus remained. Levodopa was restarted with improvement in parkinsonism and return of choreiform dyskinesia. His mother, two maternal aunts, and maternal grandfather shared similar presentations.

Results: Genetic sequencing revealed an amino acid exchange of phenylalanine to serine at codon 198. Codon 129 was heterozygous (MV). DaT-SPECT demonstrated bilaterally reduced putaminal binding.

Conclusion: This case demonstrates a comprehensive phenotype of atypical, levodopa-responsive parkinsonism with levodopa-induced dyskinesia and abnormal DaT-SPECT imaging. While the family history in this case was a clue against a sporadic condition, recognizing that multiple point mutations in the PRNP gene may mimic atypical parkinsonism can assist in identifying de novo mutations, with significant implications for genetic counseling of a patient and their relatives.

References: 1. Collins S, McLean CA, Masters CL. Gerstmann–Sträussler–Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. J Clin Neurosci. 2001;8: 387–397.
2. Plate A, Benninghoff J, Jansen GH, Wlasich E, Eigenbrod S, Drzezga A, et al. Atypical parkinsonism due to a D202N Gerstmann-Sträussler-Scheinker prion protein mutation: first in vivo diagnosed case. Mov Disord. 2013;28: 241–244.
3. Baiardi S, Rizzi R, Capellari S, Bartoletti-Stella A, Zangrandi A, Gasparini F, et al. Gerstmann-Sträussler-Scheinker disease (PRNP p.D202N) presenting with atypical parkinsonism. Neurol Genet. 2020;6: e400.
4. Malek N, Jampana R, Grosset DG. Rare case of atypical parkinsonism: why family history is important. Scott Med J. 2017;62: 159–162.
5. Dlouhy SR, Hsiao K, Farlow MR, Foroud T, Conneally PM, Johnson P, et al. Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene. Nat Genet. 1992;1: 64–67.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gerstmann-straussler-scheinker-syndrome-manifesting-levodopa-responsive-parkinsonism-levodopa-induced-dyskinesia-and-abnormal-dat-spect/