Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, invariably fatal neurodegenerative disease that usually affects patients from 35 to 55 years in age. It is exclusively heritable in an autosomal dominant manner, and is found in only a few families around the world. It was discovered by Josef Gerstmann, Ernst Sträussler, and Ilya Scheinker in 1936.

Certain symptoms are common to GSS, such as progressive ataxia, pyramidal signs, and dementia; they worsen as the disease progresses. Much like Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome has significant variety in presentation.

Symptoms and signs

Symptoms start with slowly developing dysarthria (difficulty speaking) and cerebellar truncal ataxia (unsteadiness) before the progressive dementia becomes more evident. In the early stages of GSS, people with the condition may also exhibit clumsiness and difficulty walking. As the condition progresses, symptoms of ataxia become more pronounced. Loss of memory can be the first symptom of GSS. Extrapyramidal and pyramidal symptoms and signs may occur, and the disease may mimic spinocerebellar ataxias in the beginning stages. Myoclonus (spasmodic muscle contraction) is less frequently seen than in Creutzfeldt–Jakob disease. Many patients also exhibit nystagmus (involuntary movement of the eyes), visual disturbances, and blindness or deafness. The neuropathological findings of GSS include widespread deposition of amyloid plaques composed of misfolded prion proteins.

Causes

GSS is part of a group of diseases called transmissible spongiform encephalopathies. These diseases are caused by prions, which are a class of pathogenic proteins that are resistant to proteases. These prions then form clusters in the brain, which are responsible for the neurodegenerative effects seen in patients.

The P102L mutation, which causes a substitution of proline to a leucine in codon 102, has been found in the prion protein gene (PRNP, on chromosome 20) of most affected individuals. Therefore, it appears this genetic change is usually required for the development of the disease.

Symptoms, such as clumsiness and unsteadiness when walking, appear at the beginning of the illness. Muscle jerking (myoclonus) is much less common than in Creutzfeldt-Jakob disease. Speaking becomes difficult (called dysarthria), and dementia develops. Nystagmus (rapid movement of the eyes in one direction, followed by a slower drift back to the original position) and deafness may develop. Muscle coordination is lost (called ataxia), which may cause muscles to become stiff. Usually, the muscles that control breathing and coughing are impaired, resulting in a high risk of pneumonia, which is the most common cause of death.

The disease ultimately results in death, most commonly from the patient either going into a coma, or from a secondary infection due to the patient's loss of bodily functions. GSS is a very rare TSE, making its genetic origin nearly impossible to determine. It is also challenging to find any patients with GSS, as the disease tends to be underreported, due to its clinical similarity to other diseases, and has been found in only a few countries. In 1989, the first mutation of the prion protein gene was identified in a GSS family. The largest of these families affected by GSS is the Indiana Kindred, spanning over 8 generations, and includes over 3,000 people, with 57 individuals known to be affected. GSS was later realized to have many different gene mutation types, varying in symptom severity, timing and progression. Doctors in different parts of the world are in the process of uncovering more generations and families who have the mutation.

Notes

  • Gerstmann–Sträussler–Scheinker syndrome , MedicineNet.com
  • ITALIAN ASSOCIATION AGAINST GERSTMANN STRAUSSLER SCHEINKER'S DISEASE