Rare Nephrology News

Disease Profile

Gerstmann-Straussler-Scheinker disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adult

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ICD-10

A81.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

GSSD; Gerstmann Straussler Scheinker syndrome; Cerebellar ataxia, progressive dementia, and amyloid deposits in the central nervous system;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Gerstmann-Straussler-Scheinker disease (GSS) is a type of prion disease. Prion diseases are a group of conditions that affect the nervous system. The main feature of GSS is a progressive degeneration of the cerebellum (a part of the brain that controls coordination, balance, equilibrium and muscle tone), as well as different degrees of dementia. Signs and symptoms generally develop between ages 35 and 50 years and may include weakness in the legs, poor reflexes, abnormal sensations, progressive ataxia, cognitive dysfunction, slurred speech, and spasticity. On average, people affected by GSS survive approximately 60 months (range 2 to 10 years) following diagnosis. It is caused by changes (mutations) in the PRNP gene and inheritance is autosomal dominant. Treatment is based on the signs and symptoms present in each person.[1][2]

For information on other prion diseases, please visit GARD's Creutzfeldt-Jakob disease and fatal familial insomnia pages.

Symptoms

Signs and symptoms of Gerstmann-Straussler-Scheinker disease generally develop between the ages of 35 and 50 years. Affected people may experience:[1][2][3]

  • Progressive ataxia, including clumsiness, unsteadiness, and difficulty walking
  • Cognitive dysfunction leading to bradyphrenia (slowness of thought processing) and dementia of different degrees
  • Dysarthria (slurred speech)
  • Nystagmus (abnormal eye movements)
  • Spasticity (rigid muscle tone)
  • Visual disturbances, sometimes leading to blindness
  • Lack of coordination in swallowing
  • Deafness
  • Parkinsonian features (present in some families).

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness

[ more ]

0000718
Apraxia
0002186
Areflexia
Absent tendon reflexes
0001284
Autosomal dominant inheritance
0000006
Bradykinesia
Slow movements
Slowness of movements

[ more ]

0002067
Cerebellar atrophy
Degeneration of cerebellum
0001272
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Depressivity
Depression
0000716
Dysarthria
Difficulty articulating speech
0001260
Emotional lability
Emotional instability
0000712
Gait ataxia
Inability to coordinate movements when walking
0002066
Hyperreflexia
Increased reflexes
0001347
Impaired smooth pursuit
0007772
Limb ataxia
0002070
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

0007340
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Myoclonus
0001336
Neurofibrillary tangles
0002185
Parkinsonism
0001300
Perseveration
0030223
Personality changes
Personality change
0000751
Psychosis
0000709
Rapidly progressive
Worsening quickly
0003678
Rigidity
Muscle rigidity
0002063
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Tremor
0001337
Truncal ataxia
Instability or lack of coordination of central trunk muscles
0002078
Weight loss
0001824

Cause

Gerstmann-Straussler-Scheinker disease (GSS) is caused by certain changes (mutations) in the PRNP gene.[1] PRNP encodes a protein called prion protein. Although the exact function of this protein is unknown, it appears to play an important role in the human brain and other tissues throughout the body. People affected by GSS generally have mutations in the PRNP gene that result in the production of an abnormally shaped prion protein. The abnormal protein builds up in the brain, forming clumps that damage or destroy neurons (nerve cells). This loss of brain cells leads to the signs and symptoms of GSS.[4]

Diagnosis

The diagnosis of Gerstmann-Straussler-Scheinker disease (GSS) is based on a combination of the following:[1]

  • Characteristic signs and symptoms
  • Nervous system findings including multiple amyloid plaques (clumps which form in the brain and cause the death of nerve cells and the progressive symptoms of the disease)
  • A family history consistent with autosomal dominant inheritance
  • Genetic test showing a disease-causing mutation of the PRNP gene (establishes and confirms the diagnosis).

Genetic testing for at-risk relatives who do not yet have symptoms of GSS is possible if the disease-causing mutation in the family is known. This testing is not useful in predicting age of onset, severity, type of symptoms, or rate of progression. Testing for the disease-causing mutation in the absence of definite symptoms of the disease is called predictive testing.[1]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    The treatment of Gerstmann-Straussler-Scheinker disease (GSS) is based on the signs and symptoms present in each person. There is currently no cure for the condition and no known treatments to slow its progression.[3][1]

    GeneReviews' Web site offers more specific information about the treatment and management of GSS and other genetic prion diseases.

    The National Prion Disease Surveillance Center is charged with collecting and recording all cases of prion disease in the US. They should be notified regarding all cases of suspected prion disease.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Gerstmann-Straussler-Scheinker disease. Click on the link to view a sample search on this topic.

          References

          1. Mastrianni JA. Genetic Prion Diseases. GeneReviews. January 2 2014 (retired page); https://www.ncbi.nlm.nih.gov/books/NBK1229/.
          2. Brown HG & Lee JM. Diseases of the central nervous system caused by prions. UpToDate. October 2014; https://www.uptodate.com/contents/diseases-of-the-central-nervous-system-caused-by-prions.
          3. NINDS Gerstmann-Straussler-Scheinker Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). February 13, 2007; https://www.ninds.nih.gov/Disorders/All-Disorders/Gerstmann-Straussler-Scheinker-Disease-Information-Page.
          4. PRNP. Genetics Home Reference. January 2014; https://ghr.nlm.nih.gov/gene/PRNP.

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