Gerstmann-Sträussler-Scheinker syndrome (GSS)
Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare inherited neurodegenerative disorder classified as a genetic prion disease, characterized by the abnormal accumulation of prion proteins in the brain. It is caused by mutations in the prion protein gene (PRNP) and follows an autosomal dominant inheritance pattern, giving each child of an affected parent a 50% chance of inheriting the condition. Symptoms of GSS typically manifest between the third and sixth decades of life, beginning with neurological issues such as unsteady walking, lack of coordination, and speech difficulties, eventually leading to cognitive decline, muscle tone increase, and severe physical impairment.
The disease progresses slowly, lasting anywhere from two to ten years, and often results in death due to complications such as secondary infections. Diagnosis involves advanced imaging and genetic sequencing to identify PRNP mutations, although no single test can definitively confirm GSS. Currently, there is no cure, and treatment focuses on supportive care to manage symptoms. While GSS is not contagious, it poses biohazard risks due to the nature of prion diseases, necessitating careful disposal of bodily fluids. Counseling regarding prenatal genetic testing may be available for prospective parents with a history of GSS.
Gerstmann-Sträussler-Scheinker syndrome (GSS)
- ANATOMY OR SYSTEM AFFECTED: Brain, central nervous system
- ALSO KNOWN AS: Genetic prion disease, transmissible spongiform encephalopathy
- Definition
Gerstmann-Sträussler-Scheinker (GSS) syndrome is a type of genetic prion disease. Prions are proteinaceous infectious particles that lack nucleic acid to replicate. Prion diseases may be sporadic or acquired, while a minority are inherited (10 to 15 percent). GSS syndrome is a rare, inherited neurodegenerative disorder in which an abnormal prion causes the protein amyloid to be atypically deposited in the brain. Genetic prion diseases have an incidence of one case per million persons, translating into three hundred new cases per year worldwide.
Causes
GSS syndrome is caused by a mutation in the prion protein gene PRNP. The genetic mutation is inherited in an autosomal dominant manner, meaning each child has a 50 percent chance of inheriting GSS syndrome from an affected parent. However, some mutations originate in the affected person and are considered new in that person’s family.
Risk Factors
A positive family history of GSS syndrome poses the greatest risk for inheritance of the disease. Although the disease may occur in persons of any ethnic background, prevalent mutations in those with European ancestry have been reported.
Symptoms
Symptoms gradually appear during the third to sixth decade of life. Neurological findings include an unsteady walk, a lack of muscle coordination, and speech difficulties. This often progresses to cognitive dysfunction with slower thought processing and decreased concentration, increased muscle tone, swallowing difficulties, and diminished facial expressions. Vision and hearing loss may occur. GSS syndrome progresses slowly to the final stage, when an infected person is bedridden because of worsening symptoms. The disease lasts two to ten years and ultimately results in death from a secondary infection such as pneumonia or from a urinary infection.
Screening and Diagnosis
An electroencephalogram (EEG), magnetic resonance imaging (MRI), and analysis of cerebrospinal fluid may be performed, but none of these tests can independently establish the diagnosis. Sequencing of the PRNP gene is clinically available to establish that a genetic mutation is present, but sequencing is not 100 percent accurate. Prenatal diagnosis for a pregnancy by amniocentesis or chorionic villus sampling may be available if the mutation in PRNP has been identified in an affected parent. However, testing a pregnant woman for an adult-onset disorder is controversial.
Treatment and Therapy
No cure exists for GSS syndrome. Treatment is supportive only and entails medication for clinical symptoms or a feeding tube for swallowing difficulties. Antiviral therapies are not effective.
Prevention and Outcomes
Genetic prion diseases are not directly contagious; however, bodily fluid from a person with GSS syndrome is considered a biohazard and is disposed of appropriately. Preimplantation genetic diagnosis may be available for testing embryos for a mutation in the PRNP gene before implantation through in vitro fertilization.
Bibliography
Brown, David R., ed. Neurodegeneration and Prion Disease. New York: Springer, 2005.
Gambetti, P., et al. “Inherited Prion Diseases.” In Prion Biology and Diseases, edited by Stanley B. Prusiner. 2d ed. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2004.
"Gerstmann-Straussler-Scheinker Disease." National Institute of Neurological Disorders and Stroke, 19 July 2024, www.ninds.nih.gov/health-information/disorders/gerstmann-straussler-scheinker-disease. Accessed 3 Feb. 2024.
Mastrianni, J. A. “The Genetics of Prion Diseases.” Genetics in Medicine 4 (2010): 187-195.
"Prion Disease." Cleveland Clinic, 21 Jan. 2024, my.clevelandclinic.org/health/diseases/prion-disease. Accessed 3 Feb. 2025.
Prusiner, Stanley B. “The Prion Diseases.” Scientific American 272, no. 1 (January 1995): 48-57.
Rowland, Lewis P., and Timothy A. Pedley, eds. Merritt’s Textbook of Neurology. 12th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.
Safar, J. R., et al. “Diagnosis of Human Prion Disease.” Proceedings of the National Academy of Science 102 (2005): 3501-3506.