GerstmannSträusslerScheinker

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare inherited prion disease characterized by progressive neurodegeneration caused by misfolded prion proteins. It was first described by Josef Gerstmann, Fritz Sträussler, and Ilya Scheinker in the mid-20th century. GSS is typically inherited in an autosomal dominant pattern and most cases are linked to pathogenic mutations in the PRNP gene, which encodes the prion protein. The most common mutation associated with GSS is P102L, though several other PRNP variants have been reported in affected families.

Clinically, GSS presents in adulthood, often with cerebellar symptoms such as gait and limb ataxia, and may include dysarthria and balance problems. Over time, many patients develop cognitive decline and dementia, along with pyramidal or extrapyramidal signs. The disease course is highly variable but is generally progressive, with a typical duration of two to seven years from onset. Myoclonus and prominent visual or sleep disturbances are less consistent features.

Diagnosis relies on a combination of clinical assessment and genetic testing. PRNP gene sequencing can identify pathogenic mutations. Cerebrospinal fluid testing for 14-3-3 protein is less consistently positive in GSS than in some other prion diseases. MRI often shows cerebellar and cortical atrophy, with diffusion-weighted imaging sometimes revealing restricted diffusion in affected regions. EEG findings are less characteristic than in other prion disorders. Definitive diagnosis is supported by neuropathological examination showing spongiform degeneration and PrP deposition.

There is no cure for GSS; treatment is supportive and multidisciplinary, focusing on symptom management and quality of life. Genetic counseling is recommended for at-risk relatives due to the hereditary nature of the condition.