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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
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: HPO
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
SNOMED CT: Gerstmann-Straussler-Scheinker syndrome (67155006); GSS - Gerstmann-Straussler-Scheinker syndrome (67155006)
 
Gene (location): PRNP (20p13)
OMIM®: 137440
Orphanet: ORPHA356

Disease characteristics

Excerpted from the GeneReview: Genetic Prion Diseases
Genetic prion diseases generally manifest 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. Familial Creutzfeldt-Jakob disease (fCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI) represent the core phenotypes of genetic prion disease. Note: A fourth clinical phenotype, known as Huntington disease like-1 (HDL-1) has been proposed, but this is based on a single report, and the underlying pathologic features would categorize it as GSS. Although it is clear that these four subtypes 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 ranges from the third to ninth decade of life. The course ranges from a few months to several years (typically 5-7 years; in rare instances, >10 years). [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
James A Mastrianni   view full author information

Additional descriptions

From OMIM
Gerstmann-Straussler disease 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). Gerstmann-Straussler disease 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 GHR
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.  http://ghr.nlm.nih.gov/condition/prion-disease

Clinical features

Weight loss
MedGen UID:
504965
Concept ID:
CN001653
Finding
Reduction inexisting body weight.
Impaired smooth pursuit
MedGen UID:
325176
Concept ID:
C1837458
Finding
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Depression
MedGen UID:
137999
Concept ID:
C0344315
Finding
Truncal ataxia
MedGen UID:
373078
Concept ID:
C1836397
Finding
Dysarthria
MedGen UID:
333395
Concept ID:
C1839743
Finding
Perseveration
MedGen UID:
375172
Concept ID:
C1843368
Finding
Memory impairment
MedGen UID:
368424
Concept ID:
C1963167
Finding
Tremor
MedGen UID:
776582
Concept ID:
C2364114
Finding
Psychosis
MedGen UID:
504566
Concept ID:
CN000666
Finding
A condition characterized by changes of personality and thought patterns often accompanied by hallucinations and delusional beliefs.
Emotional lability
MedGen UID:
504567
Concept ID:
CN000669
Finding
Aggressive behavior
MedGen UID:
504570
Concept ID:
CN000675
Finding
Aggressive behavior can denote verbal aggression, physical aggression against objects, physical aggression against people, and may also include aggression towards oneself.
Dementia
MedGen UID:
504574
Concept ID:
CN000683
Finding
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.
Personality changes
MedGen UID:
504584
Concept ID:
CN000707
Finding
An abnormal shift in patterns of thinking, acting, or feeling.
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Cerebellar atrophy
MedGen UID:
504781
Concept ID:
CN001166
Finding
Atrophy (wasting) of the cerebellum.
Parkinsonism
MedGen UID:
504793
Concept ID:
CN001191
Finding
Characteristic neurologic anomaly resulting form 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.
Myoclonus
MedGen UID:
504806
Concept ID:
CN001224
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Rigidity
MedGen UID:
505075
Concept ID:
CN001866
Finding
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.
Gait ataxia
MedGen UID:
505076
Concept ID:
CN001868
Finding
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.
Bradykinesia
MedGen UID:
505077
Concept ID:
CN001869
Finding
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).
Limb ataxia
MedGen UID:
505079
Concept ID:
CN001872
Finding
A kind of ataxia that affects movements of the extremities.
Neurofibrillary tangles
MedGen UID:
505147
Concept ID:
CN001981
Finding
Pathological protein aggregates formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate in an insoluble form.
Apraxia
MedGen UID:
505148
Concept ID:
CN001982
Finding
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.
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Lower limb muscle weakness
MedGen UID:
446811
Concept ID:
CN006423
Finding
Weakness of the muscles of the legs.
Lower limb muscle weakness
MedGen UID:
446811
Concept ID:
CN006423
Finding
Weakness of the muscles of the legs.

Term Hierarchy

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

Recent clinical studies

Etiology

Riudavets MA, Sraka MA, Schultz M, Rojas E, Martinetto H, Begué C, Noher de Halac I, Poleggi A, Equestre M, Pocchiari M, Sevlever G, Taratuto AL
Brain Pathol 2014 Mar;24(2):142-7. Epub 2013 Sep 19 doi: 10.1111/bpa.12083. [Epub ahead of print] PMID: 23944754
Sano K, Satoh K, Atarashi R, Takashima H, Iwasaki Y, Yoshida M, Sanjo N, Murai H, Mizusawa H, Schmitz M, Zerr I, Kim YS, Nishida N
PLoS One 2013;8(1):e54915. Epub 2013 Jan 25 doi: 10.1371/journal.pone.0054915. PMID: 23372790Free PMC Article
Takazawa T, Ikeda K, Ito H, Aoyagi J, Nakamura Y, Miura K, Iwamoto K, Kano O, Kawabe K, Iwasaki Y
Intern Med 2010;49(4):339-42. Epub 2010 Feb 15 PMID: 20154442
Collins S, McLean CA, Masters CL
J Clin Neurosci 2001 Sep;8(5):387-97. doi: 10.1054/jocn.2001.0919. PMID: 11535002
Brown P, Goldfarb LG, Brown WT, Goldgaber D, Rubenstein R, Kascsak RJ, Guiroy DC, Piccardo P, Boellaard JW, Gajdusek DC
Neurology 1991 Mar;41(3):375-9. PMID: 1672447

Diagnosis

Figini M, Alexander DC, Redaelli V, Fasano F, Grisoli M, Baselli G, Gambetti P, Tagliavini F, Bizzi A
Neuroimage Clin 2015;7:142-54. Epub 2014 Nov 29 doi: 10.1016/j.nicl.2014.11.017. PMID: 25610776Free PMC Article
Riudavets MA, Sraka MA, Schultz M, Rojas E, Martinetto H, Begué C, Noher de Halac I, Poleggi A, Equestre M, Pocchiari M, Sevlever G, Taratuto AL
Brain Pathol 2014 Mar;24(2):142-7. Epub 2013 Sep 19 doi: 10.1111/bpa.12083. [Epub ahead of print] PMID: 23944754
Karmon Y, Kurzweil A, Lindzen E, Holmlund T, Weinstock-Guttman B
J Neurol Sci 2011 Oct 15;309(1-2):55-7. Epub 2011 Aug 11 doi: 10.1016/j.jns.2011.07.028. [Epub ahead of print] PMID: 21839476
Irisawa M, Amanuma M, Kozawa E, Kimura F, Araki N
Magn Reson Med Sci 2007;6(1):53-7. PMID: 17510542
Arata H, Takashima H, Hirano R, Tomimitsu H, Machigashira K, Izumi K, Kikuno M, Ng AR, Umehara F, Arisato T, Ohkubo R, Nakabeppu Y, Nakajo M, Osame M, Arimura K
Neurology 2006 Jun 13;66(11):1672-8. doi: 10.1212/01.wnl.0000218211.85675.18. PMID: 16769939

Therapy

Torres JM, Castilla J, Pintado B, Gutiérrez-Adan A, Andréoletti O, Aguilar-Calvo P, Arroba AI, Parra-Arrondo B, Ferrer I, Manzanares J, Espinosa JC
Emerg Infect Dis 2013 Dec;19(12):1938-47. doi: 10.3201/eid1912.130106. PMID: 24274622Free PMC Article
Imberdis T, Ayrolles-Torro A, Verdier JM, Perrier V
Curr Top Med Chem 2013;13(19):2477-83. PMID: 24059332
Lukiw WJ, Dua P, Pogue AI, Eicken C, Hill JM
J Toxicol Environ Health A 2011;74(22-24):1460-8. doi: 10.1080/15287394.2011.618973. PMID: 22043907Free PMC Article
Arata H, Takashima H, Hirano R, Tomimitsu H, Machigashira K, Izumi K, Kikuno M, Ng AR, Umehara F, Arisato T, Ohkubo R, Nakabeppu Y, Nakajo M, Osame M, Arimura K
Neurology 2006 Jun 13;66(11):1672-8. doi: 10.1212/01.wnl.0000218211.85675.18. PMID: 16769939
Demiryürek D, Bayramoğlu A, Ustaçelebi S
Anat Rec 2002 Aug 15;269(4):194-7. doi: 10.1002/ar.10143. PMID: 12209557

Prognosis

Rusina R, Fiala J, Holada K, Matějčková M, Nováková J, Ampapa R, Koukolík F, Matěj R
Neurocase 2013;19(1):41-53. Epub 2012 Apr 12 doi: 10.1080/13554794.2011.654215. [Epub ahead of print] PMID: 22494260
Achury C, Camacho V, Fernández A, Gómez-Ansón B, Jaller R, Carrió I
Rev Esp Med Nucl Imagen Mol 2012 Nov-Dec;31(6):352-3. Epub 2012 May 31 doi: 10.1016/j.remn.2012.04.002. [Epub ahead of print] PMID: 23084018
Karmon Y, Kurzweil A, Lindzen E, Holmlund T, Weinstock-Guttman B
J Neurol Sci 2011 Oct 15;309(1-2):55-7. Epub 2011 Aug 11 doi: 10.1016/j.jns.2011.07.028. [Epub ahead of print] PMID: 21839476
Takazawa T, Ikeda K, Ito H, Aoyagi J, Nakamura Y, Miura K, Iwamoto K, Kano O, Kawabe K, Iwasaki Y
Intern Med 2010;49(4):339-42. Epub 2010 Feb 15 PMID: 20154442
Yang W, Cook J, Rassbach B, Lemus A, DeArmond SJ, Mastrianni JA
J Neurosci 2009 Aug 12;29(32):10072-80. doi: 10.1523/JNEUROSCI.2542-09.2009. PMID: 19675240Free PMC Article

Clinical prediction guides

Riudavets MA, Sraka MA, Schultz M, Rojas E, Martinetto H, Begué C, Noher de Halac I, Poleggi A, Equestre M, Pocchiari M, Sevlever G, Taratuto AL
Brain Pathol 2014 Mar;24(2):142-7. Epub 2013 Sep 19 doi: 10.1111/bpa.12083. [Epub ahead of print] PMID: 23944754
Torres JM, Castilla J, Pintado B, Gutiérrez-Adan A, Andréoletti O, Aguilar-Calvo P, Arroba AI, Parra-Arrondo B, Ferrer I, Manzanares J, Espinosa JC
Emerg Infect Dis 2013 Dec;19(12):1938-47. doi: 10.3201/eid1912.130106. PMID: 24274622Free PMC Article
Yang W, Cook J, Rassbach B, Lemus A, DeArmond SJ, Mastrianni JA
J Neurosci 2009 Aug 12;29(32):10072-80. doi: 10.1523/JNEUROSCI.2542-09.2009. PMID: 19675240Free PMC Article
Biernat W, Liberski PP, Guiroy DC, Yanagihara R, Gajdusek DC
Neurodegeneration 1995 Jun;4(2):195-201. PMID: 7583684
Barcikowska M, Liberski PP, Boellaard JW, Brown P, Gajdusek DC, Budka H
Acta Neuropathol 1993;85(6):623-7. PMID: 8337941

Recent systematic reviews

Capellari S, Strammiello R, Saverioni D, Kretzschmar H, Parchi P
Acta Neuropathol 2011 Jan;121(1):21-37. Epub 2010 Oct 27 doi: 10.1007/s00401-010-0760-4. [Epub ahead of print] PMID: 20978903

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