Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, usually familial, fatal neurodegenerative

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

that affects patients from 20 to 60 years in age. It is exclusively heritable, and is found in only a few families all over the world. It is, however, classified with the

transmissible spongiform encephalopathies Transmissible spongiform encephalopathies (TSEs) are a group of progressive and fatal conditions that are associated with prions and affect the brain and nervous system of many animals, including humans, cattle, and sheep. According to the most ...

(TSE) due to the causative role played by

PRNP Major prion protein (PrP), is encoded in the human by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the bod ...

, the human

prion Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...

protein. GSS was first reported by the Austrian physicians

Josef Gerstmann Josef Gerstmann (July 17, 1887, Lemberg – March 23, 1969, New York City) was a Jewish Austrian-born American neurologist. Gerstmann studied Medicine at the Medical University in Vienna, then capital of the Austro-Hungarian Empire, between 1906 ...

, Ernst Sträussler and Ilya Scheinker in 1936. Familial cases are associated with

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

-dominant inheritance. Certain symptoms are common to GSS, such as progressive

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

, pyramidal signs, and

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

; they worsen as the disease progresses.

Symptoms and signs

Symptoms start with slowly developing

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively ...

(difficulty speaking) and cerebellar

truncal ataxia Truncal ataxia (or trunk ataxia) is a wide-based "drunken sailor" gait characterised by uncertain starts and stops, lateral deviations and unequal steps. It is an instability of the trunk and often seen during sitting. It is most visible when sh ...

(unsteadiness) and then the progressive

becomes more evident. Loss of memory can be the first symptom of GSS. Extrapyramidal and pyramidal symptoms and signs may occur and the disease may mimic

spinocerebellar ataxia Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of s ...

s in the beginning stages.

Myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

(spasmodic muscle contraction) is less frequently seen than in

Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes, ...

. Many patients also exhibit

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

(involuntary movement of the eyes), visual disturbances, and even blindness or deafness. The neuropathological findings of GSS include widespread deposition of

amyloid plaques Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of micr ...

composed of abnormally folded prion protein. Four clinical phenotypes are recognized: typical GSS, GSS with areflexia and paresthesia, pure dementia GSS and Creutzfeldt-Jakob disease-like GSS.

Causes

GSS is part of a group of diseases called

. These diseases are caused by

s, which are a class of pathogenic proteins that are resistant to

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

s. These prions then form clusters in the brain, which are responsible for the neurodegenerative effects seen in patients. The P102L

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

, which causes a substitution of

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

to a

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...

codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

102, has been found in the

prion protein Major prion protein (PrP), is encoded in the human by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the bod ...

gene (''

'', on

chromosome 20 Chromosome 20 is one of the 23 pairs of chromosomes in humans. Chromosome 20 spans around 66 million base pairs (the building material of DNA) and represents between 2 and 2.5 percent of the total DNA in cells. Chromosome 20 was fully sequenced ...

) of most affected individuals. Therefore, it appears this genetic change is usually required for the development of the disease.

Diagnosis

GSS can be identified through genetic testing. Testing for GSS involves a blood and DNA examination in order to attempt to detect the mutated gene at certain codons. If the genetic mutation is present, the patient will eventually develop GSS.

Treatment

There is no cure for GSS, nor is there any known treatment to slow the progression of the disease. Therapies and medication are aimed at treating or slowing down the effects of the symptoms. The goal of these treatments is to try to improve the patient's quality of life as much as possible. There is some ongoing research to find a cure, with one of the most prominent examples being the PRN100 monoclonal antibody.

Prognosis

GSS is a disease that progresses slowly, lasting roughly 2–10 years, with an average of approximately five years. 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.

Research

Prion diseases, also called transmissible spongiform encephalopathies (TSEs), are neurodegenerative diseases of the brain thought to be caused by a protein that converts to an abnormal form called a prion. 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

External links

Gerstmann–Sträussler–Scheinker syndrome
MedicineNet.com {{DEFAULTSORT:Gerstmann-Straussler-Scheinker syndrome Rare syndromes Syndromes affecting the nervous system Transmissible spongiform encephalopathies