Gerstmann–Sträussler–Scheinker syndrome with the P102L pathogenic mutation presenting as familial Creutzfeldt–Jakob disease: a case report and review of the literature

Abstract

Gerstmann-Sträussler-Scheinker syndrome is a rare autosomal dominant disease caused by a mutation in the prion gene, usually manifesting as progressive ataxia with late cognitive decline. A 44-year-old woman with a positive family history developed early personality and behavior changes, followed by paresthesias and ataxia, later associated with memory problems, pyramidal signs, anosognosia and very late myoclonus, spasticity, and severe dysexecutive impairment. Magnetic resonance showed caudate, mesio-frontal, and insular hyper-intensities, electroencephalography revealed generalized triphasic periodic complexes. A pathogenic P102L mutation in the prion gene was detected. Our case differed from classical Gerstmann-Sträussler-Scheinker syndrome by rapid progression, severe dementia, abnormal electroencephalography and magnetic resonance findings, which were highly suggestive of familial Creutzfeldt-Jakob disease.

Clinical Variability in P102L Gerstmann–Sträussler–Scheinker Syndrome

“…This estimation is difficult to apply directly to all published cases, because of (1) the long period of data acquisition (some patients died in the 1950s, others in 2017), (2) a retrospective diagnosis in many cases, and (3) inconsistencies in prion disease surveillance in different countries. There is, however, an important argument for our observation, which is the increase in new cases reported since 2017; we found a total of 26 patients, including 6 of our 7 Czech patients (1 of our cases was published and is therefore already counted in the literature) …”

“…We focused on gender, age at onset, disease duration, onset and duration of dementia (from the onset of cognitive deterioration impacting on activities of daily living and continuing until death), onset of ataxia, MRI abnormalities (in particular basal ganglia, cortex, and cerebellum), polymorphism in codon 129, changes in deep tendon reflexes and sensory symptoms, and 14‐3‐3 protein in the CSF …”

“…The first step was to retrospectively analyze the clinical manifestation and results from auxiliary diagnostic methods (ie, brain magnetic resonance imaging [MRI], electroencephalogram [EEG], and cerebrospinal fluid [CSF] analysis) in the 7 Czech cases with postmortem confirmation. The next step was to extend this analysis by combining the data from the 7 Czech patients with data from 87 previously published P102L GSS cases, and with the use of cluster analysis, to define typical GSS syndrome phenotypes.…”

Human Prion Disorders: Review of the Current Literature and a Twenty-Year Experience of the National Surveillance Center in the Czech Republic

“…The P102L mutation was found in eight cases, and no clinically specific symptoms for this mutation were observed, although we described a case mimicking gCJD [121].…”

Detection of the GPI-anchorless prion protein fragment PrP226* in human brain

“…This unusual GSS case was caused by a classical P102L mutation, but the manifestation of the disease resembled CJD [27]. The PrP226* assay showed a fivefold higher reaction for the denatured GSS sample, compared to the average signal of other brain homogenates tested (Figure 3C, sample 22), showing a greater abundance of the PrP226* fragment in GSS brain.…”