Last updated:
8/29/2025
Years published: 2018, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Pawel P. Liberski, MD, PhD, Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland, for assistance in the preparation of this report.
Gerstmann-Sträussler-Scheinker (GSS) disease is a rare genetic degenerative brain disorder. A common symptom is a progressive loss of coordination that may present as unsteadiness of gait, difficulty walking and clumsiness. As the disease progresses, other symptoms become apparent including dementia, in which there are worsening problems with thought, cognition, memory, language and behavior.
Some people may present with psychiatric symptoms such as depression, personality change, or emotional instability before motor symptoms appear.
GSS disease is caused by changes (variants) in the prion protein (PRPN) gene. The PRNP gene encodes the human prion protein (PrPc). Variants in this gene lead to the production of abnormally shaped (misfolded) prion protein (PrPSc), also known simply as a “prion”, which is toxic to the body. In GSS disease, the abnormal prions build up primarily within the brain. This leads to the progressive loss of nerve cells (neurons) and the various symptoms associated with this disorder. GSS disease usually begins between the ages of 35 and 55 years. There is no cure, but scientists are researching ways to best treat and manage GSS disease.
Introduction
GSS disease is classified as a transmissible spongiform encephalopathy (TSE) or a prion disease. Prion diseases are caused by the accumulation of misfolded prion protein in the brain. Two other prion diseases, Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI), may also occur because of variants in the PRNP gene, although some prion diseases occur in the absence of a gene variant. Generally, prion disorders are characterized by long incubation periods and short clinical duration, which means the abnormal prions may build up for many years (long incubation period), but once symptoms begin the disorder rapidly worsens.
GSS disease is a slowly progressive condition that usually lasts from 2 to 10 years. It ultimately causes severe disability and finally death.
The symptoms, progression of the disorder and the overall severity can vary greatly among affected families and individuals. This is true even among members of the same family. The initial symptoms associated with Gerstmann-Sträussler-Scheinker disease usually include:
As the disorder progresses, affected individuals develop a condition called spasticity. Spasticity is characterized by rigid muscle tone and progressive muscle stiffness and weakness, causing abnormal, writhing movements and abnormal slowness of movement (bradykinesia). Some people may exhibit a reduced degree of facial expression called hypomimia or masked facies. Hypomimia means that the person does not show much expression or emotion.
Some affected people develop rapid, involuntary eye movements (nystagmus), have difficulty judging distance or scale (ocular dysmetria) and have problems with vision that may progress to blindness. Less commonly, hearing loss or deafness will develop.
Additional symptoms that sometimes occur include:
Eventually, affected individuals develop problems with cognition, which is thinking, remembering, reasoning, imagining and processing thoughts. Concentration and focus are particularly affected, and some individuals exhibit slowness of thought processing (bradyphrenia). As the disease progresses, other symptoms become apparent including dementia, in which there are worsening problems with thought, cognition, memory, language and behavior. Initially, the signs may be subtle and include unintended weight loss, forgetfulness, inattentiveness, problems concentrating, or speech problems. Episodes of confusion or hallucinations can eventually occur.
In a few people, psychiatric problems occur first, before other symptoms of the disease. Some people may be misdiagnosed with schizophrenia.
GSS disease causes slowly progressive physical and mental deterioration, although more rapid progression can occur. Eventually, affected people become bedridden, unable to eat unassisted and unable to communicate. The disease ultimately progresses to coma and death.
GSS disease is caused by changes (variants) in the PRNP gene. Genes provide instructions for encoding proteins that play a critical role in many functions of the body. When a variant of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the protein, this can affect many organ systems of the body, including the brain.
The PRNP gene encodes for a protein called prion protein, a cellular variant or PrPc. The exact function of PrPc in the body is not fully understood. However, because of the variant gene, the PrPSc that is produced develops an abnormal 3-dimensional shape that is described simply as “misfolded”. The misfolded PrPSc is toxic to the body, especially cells of the nervous system. In GSS disease, misfolded PrPSc is found in many brain structures, mostly the cerebellum and also in the thalamus, which is a structure deep within the brain that helps regulate many functions of the body including sleep, appetite and body temperature. As the misfolded PrPSc builds up, it results in a progressive destruction of nerve cells (neurons), which leads to symptoms of the disorder. The damage to brain tissue may appear as sponge-like cavities or spaces (vacuoles) when examined under a microscope, which is why prion diseases like GSS disease are called transmissible spongiform encephalopathies.
The term “prion” was coined to designate a “proteinaceous infectious agent” to explain the protein-only nature of the infectious agent. Extensive research has shown that a prion is essentially the misfolded PrPSc. However, it is important to know that GSS disease is not contagious in the traditional sense because the only way to transmit prion disease to a healthy individual is through direct exposure to disease-affected brain tissue, for instance by injection. If a person without an underlying gene variant develops a prion disease by transmission from another prion disease, they are said to have an ‘acquired’ form. For example, variant Creutzfeldt-Jakob disease occurred in the United Kingdom when people ate prion-contaminated beef. A lesser-known example is kuru. Kuru is a virtually extinct prion disease that occurred in the Fore people of Papua New Guinea. The disease spread throughout this population because of the villagers’ practice of eating the brains of deceased kuru-affected tribesmen (ritualistic cannibalism).
The most common gene variant seen in people with GSS disease is called P102L. However, researchers have discovered many other variants that can also cause the condition.
GSS is inherited as an autosomal dominant disorder. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Researchers think that GSS disease is associated with almost complete penetrance, which means that virtually all individuals who have a disease-causing variant in the PRPN gene will eventually develop signs and symptoms of the disorder.
The exact incidence or prevalence of GSS disease is unknown. Estimates range from 1 to 10 in 100,000,000 people in the general population. CJD affects about 1 in 1,000,000 people in the general population per year. Genetic prion diseases are believed to make up about 15% of all individuals with prion diseases. Because rare diseases often go undiagnosed or misdiagnosed, it is difficult to determine their true frequency in the general population. GSS affects males and females in equal numbers. The average age of onset is 35-50 years old, and the youngest person described in the medical literature with GSS disease was a 10-year-old child.
A diagnosis of GSS disease is based upon identification of characteristic symptoms, a detailed patient history, thorough clinical evaluation and a variety of specialized tests. A diagnosis of GSS disease cannot be confirmed through laboratory tests or imaging studies.
Molecular genetic testing can confirm a diagnosis of GSS disease when a disease-causing variant in the PRPN gene is detected. Genetic testing may be ordered earlier in the diagnostic workup in people with unexplained psychiatric and coordination symptoms who also have a family history of the disorder.
Clinical Testing and Workup
Doctors may recommend an electroencephalogram (EEG), which is a test that measures the electrical activity of the brain and may show changes in brain function and slowing of background activity. An EEG can also be used to help to detect seizures.
Advanced imaging techniques include computerized tomography (CT) scanning and magnetic resonance imaging (MRI) may be conducted. CT scanning is not useful in the diagnosis of GSS disease or other prion disease, while the MRI can show some abnormalities in the scan that may support prion disease, although its application to diagnose GSS disease is not well characterized. However, MRI and CT may be helpful in ruling out other conditions that may mimic GSS disease or other prion diseases. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and body tissues.
Single photon emission computed tomography (SPECT) is a specialized form of CT scanning that may show reduced blood flow in the brain in some people with GSS disease, particularly early in the disease. SPECT can show how blood flows to tissues and organs. SPECT uses a radioactive material called a tracer. This chemical tracer is injected into the body and emits gamma rays that are recorded by a computer. Sometimes this test can demonstrate slow or inadequate flow of blood through blood vessels (hypoperfusion), potentially resulting in decreased supply of oxygen and nutrients.
A brain biopsy should only be considered if doctors suspect a condition that can be treated and needs to be confirmed as part of the possible diagnoses.
Treatment
There is no cure for GSS disease or other prion related diseases. Treatment of GSS disease is directed toward the management of specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Neurologists, psychiatrists, psychologists, pain specialists, social workers and other healthcare professionals may need to work in a coordinated way as a team for the best treatment plan. Psychosocial support for the entire family is essential as well. Genetic counseling may be recommended for affected individuals and their families.
There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with GSS disease.
Affected individuals may receive standard treatments for any associated symptoms. Antiseizure medications, known as anti-epileptics or anti-convulsants, may be prescribed. A drug called clonazepam may be used to treat myoclonus. Psychiatric symptoms like depression or psychosis may be treated with antidepressants or neuroleptics. Muscle rigidity might be eased with dopamine-based treatments and antispastic medications are used for spasticity.
Physical and occupational therapy aims to prevent complications like contractures and to improve daily function and safety. Nutritionists and speech pathologists assist with feeding and communication challenges. If swallowing problems are severe enough, families can consider the option of a feeding tube. A feeding tube is a device that is inserted through a small surgical cut in the abdominal wall directly into the stomach. This ensures that the person receives sufficient calories and nutrients.
Given the rapid progression of the disease, affected people require close monitoring by their doctor, typically every two weeks, to reassess symptoms and adjust care as needed.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Chen Z, Guo J, Ran N, Zhong Y, Yang F, Sun H. A family with mental disorder as the first symptom finally confirmed with Gerstmann-Sträussler-Scheinker disease with P102L mutation in PRNP gene – case report. Prion. 2023;17(1):37-43. doi:10.1080/19336896.2023.2180255
Mercer RCC, Daude N, Dorosh L, et al. A novel Gerstmann-Straussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa Prp fragments and reveals N-terminal structural changes shared by other GSS alleles. PLoS Pathog. 2018;14:e10006826. https://www.ncbi.nlm.nih.gov/pubmed/29338055
Smid J, Studart A Neto, Landemberger MC, et al. High phenotypic variability in Gerstmann-Straussler-Scheinker diseasea. Arq Neuropsiquiatr. 2017;75:331-338. https://www.ncbi.nlm.nih.gov/pubmed/28658400
Keuss SE, Ironside JW, O’Riordan J. Gerstmann-Straussler-Scheinker disease with atypical presentation. BMJ Case Rep. 2017;2017. https://www.ncbi.nlm.nih.gov/pubmed/29092967
Burchell JT, Panegyres PK. Prion diseases: immunotargets and therapy. Immunotargets Ther. 2016;5:57-68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970640/
Pirisinu L, Di Bari MA, D’Agostino C, et al. Gerstmann-Straussler-Scheinker disease subtypes efficiently transmit in bank voles as genuine prion diseases. Sci Rep. 2016;6:20443. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740801/
Geschwind MD. Prion diseases. Continuum (Minneap Minn). 2015;21:1612-1638. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879966/
Liberski PP, Surewicz WK. Molecular genetics of Gerstmann-Straussler-Scheinker disease and Creutzfeldt-Jakob disease. Genetics. 2013;2:2. https://www.omicsonline.org/molecular-genetics-of-gerstmann-straussler-scheinker-disease-and-creutzfeld-jakob-disease-2161-1041.1000117.pdf
Liberski PP. Historical overview of prion diseases: a view from afar. Folia Neuropathol. 2012;50:1-12. https://www.ncbi.nlm.nih.gov/pubmed/22505359
Holman RC, Belay ED, Christensen KY, et al. Human pion disease in the United States. PLoS One. 2010;5:e8521. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797136/
INTERNET
Zerr I, Schmitz M. Genetic Prion Disease. 2003 Mar 27 [Updated 2021 Jan 7]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1229/ Accessed August 28, 2025.
Appleby BS, Cohen ML Diseases of the central nervous system caused by prions. UpToDate. Mar 18, 2024. Available at: https://www.uptodate.com/contents/diseases-of-the-central-nervous-system-caused-by-prions Accessed August 28, 2025.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:137440; Last Update:01/11/2023. Available at: https://www.omim.org/entry/137440 Accessed August 28, 2025.
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