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Gerstmann-Straussler-Scheinker syndrome(GSD)

MedGen UID:
4886
Concept ID:
C0017495
Disease or Syndrome
Synonyms: Amyloidosis cerebral with spongiform encephalopathy; CEREBELLAR ATAXIA, PROGRESSIVE DEMENTIA, AND AMYLOID DEPOSITS IN CNS; Cerebellar ataxia, progressive dementia, and amyloid deposits in the central nervous system; Encephalopathy subacute spongiform Gerstmann-Straussler type; GERSTMANN-STRAUSSLER DISEASE; Gerstmann-Straussler-Scheinker Disease; GSD; PRION DEMENTIA; Spinocerebellar ataxia and plaque-like deposits; Spongiform encephalopathy
SNOMED CT: Gerstmann-Straussler-Scheinker syndrome (67155006); GSS - Gerstmann-Straussler-Scheinker syndrome (67155006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): PRNP (20p13)
 
Monarch Initiative: MONDO:0007656
OMIM®: 137440
Orphanet: ORPHA356

Disease characteristics

Excerpted from the GeneReview: Genetic Prion Disease
Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome. [from GeneReviews]
Authors:
Inga Zerr  |  Matthias Schmitz   view full author information

Additional descriptions

From OMIM
Gerstmann-Straussler disease (GSD) is a rare inherited prion disease characterized by adult onset of memory loss, dementia, ataxia, and pathologic deposition of amyloid-like plaques in the brain (Gerstmann et al., 1936). GSD typically presents with progressive limb and truncal ataxia, dysarthria, and cognitive decline in the thirties and forties, and the average disease duration is 7 years. GSD can be distinguished from CJD by earlier age at onset, longer disease duration, and prominent cerebellar ataxia (Masters et al., 1981). On the basis of clinical and pathologic criteria, Hsiao et al. (1989) suggested that Gerstmann-Straussler syndrome could be classified into 3 forms: an 'ataxic' form, a 'dementing' form, and a dementing form that is accompanied by pathologic quantities of neurofibrillary tangles (NFTs). However, these distinctions may only underscore the phenotypic variability in presentation and progression of the disease (Panegyres et al., 2001). PRNP-related amyloid angiopathy is usually not a feature of CJD, GSD, or FFI. However, PRNP-immunoreactive amyloid deposits within the walls of cerebral vessels have been observed in patients with truncating mutations in the PRNP gene. Data suggest that C-terminal-truncated PRNP proteins lacking the glycosylphosphatidylinositol (GPI) anchor required to attach the protein to the plasma membrane may readily form amyloid fibrils that result in cerebrovascular amyloid deposition (summary by Revesz et al., 2009).  http://www.omim.org/entry/137440
From MedlinePlus Genetics
Prion disease represents a group of conditions that affect the nervous system in humans and animals. In people, these conditions impair brain function, causing changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements, particularly difficulty with coordinating movements (ataxia). The signs and symptoms of prion disease typically begin in adulthood and worsen with time, leading to death within a few months to several years.  https://medlineplus.gov/genetics/condition/prion-disease

Clinical features

From HPO
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Neurofibrillary tangles
MedGen UID:
39273
Concept ID:
C0085400
Finding
Pathological protein aggregates formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate in an insoluble form.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Perseverative thought
MedGen UID:
66686
Concept ID:
C0233651
Mental or Behavioral Dysfunction
Manifestations of perseverative thoughts are behaviors that do not meet the demands of the situation, are not the product of deliberation, and may unfold despite counter intention.
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Impaired smooth pursuit
MedGen UID:
325176
Concept ID:
C1837458
Finding
An impairment of the ability to track objects with the ocular smooth pursuit system, a class of rather slow eye movements that minimizes retinal target motion.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Gerstmann-Straussler-Scheinker syndrome in Orphanet.

Professional guidelines

PubMed

Zerr I, Villar-Piqué A, Schmitz VE, Poleggi A, Pocchiari M, Sánchez-Valle R, Calero M, Calero O, Baldeiras I, Santana I, Kovacs GG, Llorens F, Schmitz M
Biomolecules 2019 Nov 28;9(12) doi: 10.3390/biom9120800. PMID: 31795176Free PMC Article
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Lancet 1994 Jan 15;343(8890):181-2. doi: 10.1016/s0140-6736(94)90977-6. PMID: 7904034

Recent clinical studies

Etiology

Piñar-Morales R, Barrero-Hernández F, Aliaga-Martínez L
Med Clin (Barc) 2023 Jun 23;160(12):554-560. Epub 2023 Apr 21 doi: 10.1016/j.medcli.2023.03.001. PMID: 37088611
Baldwin KJ, Correll CM
Semin Neurol 2019 Aug;39(4):428-439. Epub 2019 Sep 18 doi: 10.1055/s-0039-1687841. PMID: 31533183
Asher DM, Gregori L
Handb Clin Neurol 2018;153:1-17. doi: 10.1016/B978-0-444-63945-5.00001-5. PMID: 29887130
Geschwind MD
Continuum (Minneap Minn) 2015 Dec;21(6 Neuroinfectious Disease):1612-38. doi: 10.1212/CON.0000000000000251. PMID: 26633779Free PMC Article
Huang WJ, Chen WW, Zhang X
Eur Rev Med Pharmacol Sci 2015 Nov;19(21):4028-34. PMID: 26592824

Diagnosis

Piñar-Morales R, Barrero-Hernández F, Aliaga-Martínez L
Med Clin (Barc) 2023 Jun 23;160(12):554-560. Epub 2023 Apr 21 doi: 10.1016/j.medcli.2023.03.001. PMID: 37088611
Baldwin KJ, Correll CM
Semin Neurol 2019 Aug;39(4):428-439. Epub 2019 Sep 18 doi: 10.1055/s-0039-1687841. PMID: 31533183
Asher DM, Gregori L
Handb Clin Neurol 2018;153:1-17. doi: 10.1016/B978-0-444-63945-5.00001-5. PMID: 29887130
Geschwind MD
Continuum (Minneap Minn) 2015 Dec;21(6 Neuroinfectious Disease):1612-38. doi: 10.1212/CON.0000000000000251. PMID: 26633779Free PMC Article
Huang WJ, Chen WW, Zhang X
Eur Rev Med Pharmacol Sci 2015 Nov;19(21):4028-34. PMID: 26592824

Therapy

Contiliani DF, Ribeiro YA, de Moraes VN, Pereira TC
Cells 2021 Jun 29;10(7) doi: 10.3390/cells10071620. PMID: 34209482Free PMC Article
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Demiryürek D, Bayramoğlu A, Ustaçelebi S
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Prognosis

Piñar-Morales R, Barrero-Hernández F, Aliaga-Martínez L
Med Clin (Barc) 2023 Jun 23;160(12):554-560. Epub 2023 Apr 21 doi: 10.1016/j.medcli.2023.03.001. PMID: 37088611
Schmitz M, Villar-Piqué A, Hermann P, Escaramís G, Calero M, Chen C, Kruse N, Cramm M, Golanska E, Sikorska B, Liberski PP, Pocchiari M, Lange P, Stehmann C, Sarros S, Martí E, Baldeiras I, Santana I, Žáková D, Mitrová E, Dong XP, Collins S, Poleggi A, Ladogana A, Mollenhauer B, Kovacs GG, Geschwind MD, Sánchez-Valle R, Zerr I, Llorens F
Brain 2022 Apr 18;145(2):700-712. doi: 10.1093/brain/awab350. PMID: 35288744Free PMC Article
Rudge P, Jaunmuktane Z, Hyare H, Ellis M, Koltzenburg M, Collinge J, Brandner S, Mead S
Brain 2019 Mar 1;142(3):760-770. doi: 10.1093/brain/awy358. PMID: 30698738Free PMC Article
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Sci Rep 2017 Sep 6;7(1):10655. doi: 10.1038/s41598-017-10922-w. PMID: 28878311Free PMC Article
Weissmann C, Flechsig E
Br Med Bull 2003;66:43-60. doi: 10.1093/bmb/66.1.43. PMID: 14522848

Clinical prediction guides

Lukiw WJ
Biomolecules 2022 Jan 20;12(2) doi: 10.3390/biom12020166. PMID: 35204666Free PMC Article
Popova SN, Tarvainen I, Capellari S, Parchi P, Hannikainen P, Pirinen E, Haapasalo H, Alafuzoff I
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Weissmann C, Flechsig E
Br Med Bull 2003;66:43-60. doi: 10.1093/bmb/66.1.43. PMID: 14522848
Brandel JP
Biomed Pharmacother 1999;53(1):14-8. doi: 10.1016/s0753-3322(99)80055-9. PMID: 10221163

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