Gerstmann–Sträussler–Scheinker Syndrome: The Spongy Brain Syndrome

Summary of Disease

GSS is a prion disease, classified specifically as a transmissible spongiform encephalopathy (TSE), that leads to the progressive degeneration of the cerebellum, as well as degrees of dementia.¹ Prion diseases are a group of disorders caused by mutated and misfolded proteins that accumulate in the brain over time.¹ GSS is classified specifically as a transmissible spongiform encephalopathy (TSE), which means it is a transmissible disease that causes damage to the brain, causing the brain to have a sponge-like appearance.¹ GSS is inherited in an autosomal dominant fashion which is unique as compared to other diseases classified as TSEs.¹ GSS is generally developed between the ages 35-50, with the youngest discovery in a 10-year old child.² It is difficult to diagnose GSS because clinical symptoms, such as reduced coordination and impaired speech, do not appear until significant disease progression.

Etiology & Pathology

GSS, as well as two other similar prion diseases called Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI), is caused by mutations in the PRNP gene, which encodes for the PrP protein.³ The exact function of PrP protein is unknown, but it has been localized to the brain. The hypothetical function is to transport copper into cells and protect neurons from injury.⁴ Due to these mutations, the PRNP gene encodes for a misfolded version of the PrP protein. This misfolded PrP protein, called the PrPSc, is harmful to the body because it clumps up in various parts of the brain, specifically within the cerebellum and the thalamus.⁴ Initially, the clumps of the misfolded protein do not have a detrimental effect on the brain; however, they eventually start to block neuronal connections. The severing of connections eventually leads to rapid neuronal death.²

Symptoms

As mentioned before, the small clumps that form during the onset of the disease do not have a significant detrimental impact on the brain, so there are virtually no symptoms during the early stages of GSS. However, once the clumps start to significantly impact neuronal activity, numerous symptoms begin to appear.¹ Prominent symptoms include ataxia, which disrupts balance and other voluntary movements, and slurred speech.¹ There have also been cases of patients developing dementia.³ As with most neurodegenerative diseases, GSS causes progressive physical and mental deterioration.²

Diagnoses

GSS can be diagnosed by identifying symptoms and reviewing a detailed patient history. Diagnosis can be supported through further investigations such as an electroencephalogram (EEG) to examine any changes in brain function by measuring the electrical activity of the brain.¹ Confirmation of diagnosis can be achieved through molecular genetic testing to determine the presence of the mutated gene.¹ A combination of these practices helps doctors determine that a patient specifically has GSS as opposed to other neurodegenerative diseases or other similar prion diseases such as CJD or FFI. Furthermore, since GSS is an inherited disease, it is possible for individuals to undergo predictive testing by taking a genetic test to see whether they have the PRNP gene mutation.¹ Although this testing will not predict any other factors such as the age of onset, it can help predict whether an individual will develop GSS in the future since researchers found that nearly everyone with the PRNP mutation will eventually develop the disorder.²

Treatment

As with many other neurodegenerative diseases, scientists have not been able to find a cure for GSS. After patients begin experiencing the symptoms of GSS, the rapid physical and mental deterioration soon causes them to become bedridden. Eventually, they will go into a coma which will be non-reversible and lead to death.¹ Most patients pass away approximately five years after being diagnosed with the disorder, with almost everyone passing away between two to ten years after diagnosis.² Although there is no treatment to delay or prevent the effects of GSS, there exists treatment to help patients manage symptoms of the disorder.⁵ A multi-disciplinary team of professionals including neurologists, psychologists, psychiatrists, and other health professionals work together to plan proper and individualized treatment for the patient.

Current Research

In order to expand more on the treatment for GSS, further research focused on treatment trials is required.¹ There are also advocacy groups and support organizations centered on GSS to aid in raising awareness of the disease, furthering research, and supporting patients and their families.⁵ Even though not much is known about treating GSS, studying the patients who suffer from the disease can provide considerable insight. Further studies focused on prion diseases at large are required to further elucidate the nuances of these rare but certainly devastating diseases.

Sreethan Vuppula

References:

1. Gerstmann-Sträussler-Scheinker disease. NORD (National Organization for Rare Disorders). Published February 23, 2019. https://rarediseases.org/rare-diseases/gerstmann-straussler-scheinker-disease/.

2. Gerstmann-Straussler-Scheinker disease. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/7690/gerstmann-straussler-scheinker-disease.

3. Transmissible spongiform encephalopathies information page. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Transmissible-Spongiform-Encephalopathies-Information-Page.

4. PRNP gene: Medlineplus Genetics. MedlinePlus. Published August 18, 2020. https://medlineplus.gov/genetics/gene/prnp/.

5. Gerstmann-Straussler-Scheinker syndrome. Treatment: Gerstmann-Straussler-Scheinker syndrome. https://rarediseases.oscar.ncsu.edu/disease/gerstmann-straussler-scheinker-syndrome/communities/#disease-specific-communities.

Cite This Article:

Vuppala S., Sharma D., Charron B., Chharawala V., Merchant A., Lombo L. Gerstmann–Sträussler–Scheinker Syndrome: The Spongy Brain Syndrome. Illustrated by E. Jung. Rare Disease Review. April 2022. DOI:10.13140/RG.2.2.23245.72164.