GERSTMANN-STRÄUSSLER-SCHEINKER SYNDROME: Difference between revisions
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{{Gerstmann-Sträussler-Scheinker syndrome}} | {{Gerstmann-Sträussler-Scheinker syndrome}} | ||
{{CMG}} | {{CMG}} '''Associate Editor(s)-in-Chief''':{{VSRN}} | ||
==[[Gerstmann-Sträussler-Scheinker syndromeoverview|Epidemiology]]== | ==[[Gerstmann-Sträussler-Scheinker syndromeoverview|Epidemiology]]== | ||
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The high penetrance autosomal-dominant pattern of GSS is inherited by a combination of insertion mutations in the octapeptide repeat and several point mutations. Around the world, at least 24 distinct kindreds have been recognized. P102L is the most prevalent mutation.<ref name="PMID: 2564168">{{cite journal |vauthors=Hsiao K,|title= Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome . |PMID=2564168 |url=}}</ref><ref name="PMID: 1348851.">{{cite journal |vauthors=Kretzschmar HA,|title= Prion protein mutation at codon 102 in an Italian family with Gerstmann-Sträussler-Scheinker syndrome. |PMID=1348851. |url=}}</ref> | The high penetrance autosomal-dominant pattern of GSS is inherited by a combination of insertion mutations in the octapeptide repeat and several point mutations. Around the world, at least 24 distinct kindreds have been recognized. P102L is the most prevalent mutation.<ref name="PMID: 2564168">{{cite journal |vauthors=Hsiao K,|title= Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome . |PMID=2564168 |url=}}</ref><ref name="PMID: 1348851.">{{cite journal |vauthors=Kretzschmar HA,|title= Prion protein mutation at codon 102 in an Italian family with Gerstmann-Sträussler-Scheinker syndrome. |PMID=1348851. |url=}}</ref> | ||
==[[Gerstmann-Sträussler-Scheinker | ==[[Gerstmann-Sträussler-Scheinker syndromepathophysiology|Pathophysiology]]== | ||
Multicentric amyloid plaques in the brain's cerebral cortex, basal ganglia, cerebellum, and other areas are indicative of glioblastoma-related syndromes (GSS). While prevalent, speziform degeneration is not always evident. Brains from various kinds have been shown to have neurofibrillary tangles and neuropil threads, which are the same as those observed in Alzheimer's disease. Protease-resistant C- and N-terminally truncated fragments are a hallmark of Creutzfeldt-Jakob disease (CJD), although the biochemical characteristics of prion protein (PrP) are different.<ref name="PMID: 8059606.">{{cite journal |vauthors=Guiroy DC,|title= elationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, Creutzfeldt-Jakob disease and Gerstmann-Sträussler syndrome. |PMID=8059606. |url=}}</ref> | |||
==[[Gerstmann-Sträussler-Scheinker syndromecauses|Clinical features]]== | |||
Although the development of symptoms in older individuals has been documented, the clinical characteristic is progressive cerebellar degeneration and/or parkinsonism accompanied by variable degrees of dementia in patients nearing midlife (mean age 43 to 48 years). | |||
Incoordination, ataxia of the gait, and clumsiness are examples of cerebellar symptoms. Other early symptoms include proximal weakness in the legs, hyporeflexia, and dysesthesia. In GSS, myoclonus usually doesn't happen or happens later in the disease. The onset and severity of dementia differs among impacted families and members of the same family.<ref name="PMID: 1672447.">{{cite journal |vauthors=Brown P,|title= Clinical and molecular genetic study of a large German kindred with Gerstmann-Sträussler-Scheinker syndrome. Neurology. |PMID=1672447. |url=}}</ref> <ref name="PMID: 7767492.">{{cite journal |vauthors=Ghetti B |title= Gerstmann-Sträussler-Scheinker disease and the Indiana kindred. Brain Pathol. Neurology. |PMID=7767492.|url=}}</ref> <ref name="PMID: 9869672.">{{cite journal |vauthors=Johnson RT |title= Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. Brain Pathol. Neurology. |PMID=9869672.|url=}}</ref> | |||
Incoordination, ataxia of the gait, and clumsiness are examples of cerebellar symptoms. Other early symptoms include proximal weakness in the legs, hyporeflexia, and dysesthesia. In GSS, myoclonus usually doesn't happen or happens later in the disease. The onset and severity of dementia differs among impacted families and members of the same family. <ref name="PMID:16769939.">{{cite journal |vauthors=Arata H |title= Early clinical signs and imaging findings in Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu). Brain Pathol. Neurology. |PMID=16769939..|url=}}</ref> | |||
Variations in the underlying PRNP mutation are partly responsible for the illness's diversity in expression. Patients with A117V, Y145STOP, and F198S mutations may have dementia predominating, whereas patients with GSS who carry the P102L mutation exhibit more significant cerebellar symptoms <ref name="PMID: 1348851.">{{cite journal |vauthors=Kretzschmar HA |title= Prion protein mutation at codon 102 in an Italian family with Gerstmann-Sträussler-Scheinker syndrome. Brain Pathol. Neurology. |PMID= 1348851.|url=}}</ref>. For GSS individuals who have the P102L mutation, polymorphism at codon 129 could potentially have a moderating effect. But given that affected families with similar gene mutations exhibit different clinical manifestations of various illnesses, it is likely that additional unknown variables play a role.<ref name="PMID: 18757886.">{{cite journal |vauthors=Webb TE |title= Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series. Brain Pathol. Neurology. |PMID= 18757886.|url=}}</ref> <ref name="PMID: 8797472.">{{cite journal |vauthors=Barbanti P |title= Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Sträussler-Scheinker disease. Brain Pathol. Neurology. |PMID= 8797472.|url=}}</ref> | |||
Usually, the sickness progresses for around five years until it finally results in death.<ref name="PMID: 22411239.">{{cite journal |vauthors=Barbanti P |title= Gerstmann-Sträussler-Scheinker disease. Brain Pathol. Neurology. |PMID= 22411239.|url=}}</ref> | |||
==[[Gerstmann-Sträussler-Scheinker syndrome diagnosis]]== | |||
Given that PRNP gene mutations have been identified in every patient with confirmed GSS, demonstrating these mutations provides a sensitive and specific method of diagnosing GSS. One lady with a family history of GSS was able to undergo preimplantation genetic testing before in vitro fertilization with success.<ref name="PMID: 24493558.">{{cite journal |vauthors=Uflacker A |title= Preimplantation genetic diagnosis (PGD) for genetic prion disorder due to F198S mutation in the PRNP gene. Brain Pathol. Neurology. |PMID= 24493558.|url=}}</ref> | |||
Biopsy- A curable illness should only be included in the clinical differential diagnosis before considering brain biopsy. | |||
RT-QuIC-Compared to sporadic CJD (sCJD), laboratory and imaging investigations are less useful in the diagnosis of GSS. Normal cerebrospinal fluid (CSF) 14-3-3 and tau findings are seen in most GSS patients. Real-time quaking-induced conversion (RT-QuIC) testing in GSS is less sensitive than sCJD, even if certain instances show positive results.The electroencephalogram (EEG) may show slowing but does not typically show the periodic sharp wave complexes characteristic of sCJD.<ref name="PMID: 28878311.">{{cite journal |vauthors=Franceschini A |title= High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions. Brain Pathol. Neurology. |PMID= 28878311.|url=}}</ref> | |||
== | MRI- Although the results of brain magnetic resonance imaging (MRI) are neither sensitive or specific, they can reveal regions of reduced T2 signal in the midbrain and striatum in some individuals, as well as nonspecific cerebellar and/or cortical atrophy on structural neuroimaging [154]. Patients with GSS seldom show hyperintensity on diffusion-weighted imaging (DWI) and/or fluid-attenuated inversion recovery (FLAIR) sequences in the cortical ribbon and/or basal ganglia, which is a typical finding in sCJD. <ref name="PMID: 8454765.">{{cite journal |vauthors=Wimberger D |title= Gerstmann-Sträussler-Scheinker syndrome: MR findings.. Brain Pathol. Neurology. |PMID= 8454765.|url=}}</ref> | ||
==[[Gerstmann-Sträussler-Scheinker | ==[[Gerstmann-Sträussler-Scheinker syndrome management]]== | ||
There isn't a particular GSS therapy that has been demonstrated to enhance results. In general, management is encouraging. | |||
== | Two GSS patients who participated in an observational research utilizing intraventricular pentosan polysulfate may have had longer survival; however, this finding may not have therapeutic importance because prolonged longevity has also been noted in individuals who are not receiving treatment.<ref name="PMID:18355301.">{{cite journal |vauthors=Bone I |title= Intraventricular pentosan polysulphate in human prion diseases: an observational study in the UK. Eur J Brain Pathol. Neurology. |PMID= 18355301.|url=}}</ref> | ||
==[[ | ==[[ References]]== | ||
Latest revision as of 22:31, 25 June 2024
Template:Gerstmann-Sträussler-Scheinker syndrome
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:Rithish Nimmagadda,MBBS.[2]
Epidemiology
A rare inherited human prion illness called Gerstmann-Sträussler-Scheinker syndrome (GSS) affects 1 to 10 people out of every 100 million people annually.
The high penetrance autosomal-dominant pattern of GSS is inherited by a combination of insertion mutations in the octapeptide repeat and several point mutations. Around the world, at least 24 distinct kindreds have been recognized. P102L is the most prevalent mutation.[1][2]
Pathophysiology
Multicentric amyloid plaques in the brain's cerebral cortex, basal ganglia, cerebellum, and other areas are indicative of glioblastoma-related syndromes (GSS). While prevalent, speziform degeneration is not always evident. Brains from various kinds have been shown to have neurofibrillary tangles and neuropil threads, which are the same as those observed in Alzheimer's disease. Protease-resistant C- and N-terminally truncated fragments are a hallmark of Creutzfeldt-Jakob disease (CJD), although the biochemical characteristics of prion protein (PrP) are different.[3]
Clinical features
Although the development of symptoms in older individuals has been documented, the clinical characteristic is progressive cerebellar degeneration and/or parkinsonism accompanied by variable degrees of dementia in patients nearing midlife (mean age 43 to 48 years).
Incoordination, ataxia of the gait, and clumsiness are examples of cerebellar symptoms. Other early symptoms include proximal weakness in the legs, hyporeflexia, and dysesthesia. In GSS, myoclonus usually doesn't happen or happens later in the disease. The onset and severity of dementia differs among impacted families and members of the same family.[4] [5] [6]
Incoordination, ataxia of the gait, and clumsiness are examples of cerebellar symptoms. Other early symptoms include proximal weakness in the legs, hyporeflexia, and dysesthesia. In GSS, myoclonus usually doesn't happen or happens later in the disease. The onset and severity of dementia differs among impacted families and members of the same family. [7]
Variations in the underlying PRNP mutation are partly responsible for the illness's diversity in expression. Patients with A117V, Y145STOP, and F198S mutations may have dementia predominating, whereas patients with GSS who carry the P102L mutation exhibit more significant cerebellar symptoms [2]. For GSS individuals who have the P102L mutation, polymorphism at codon 129 could potentially have a moderating effect. But given that affected families with similar gene mutations exhibit different clinical manifestations of various illnesses, it is likely that additional unknown variables play a role.[8] [9]
Usually, the sickness progresses for around five years until it finally results in death.[10]
Gerstmann-Sträussler-Scheinker syndrome diagnosis
Given that PRNP gene mutations have been identified in every patient with confirmed GSS, demonstrating these mutations provides a sensitive and specific method of diagnosing GSS. One lady with a family history of GSS was able to undergo preimplantation genetic testing before in vitro fertilization with success.[11]
Biopsy- A curable illness should only be included in the clinical differential diagnosis before considering brain biopsy.
RT-QuIC-Compared to sporadic CJD (sCJD), laboratory and imaging investigations are less useful in the diagnosis of GSS. Normal cerebrospinal fluid (CSF) 14-3-3 and tau findings are seen in most GSS patients. Real-time quaking-induced conversion (RT-QuIC) testing in GSS is less sensitive than sCJD, even if certain instances show positive results.The electroencephalogram (EEG) may show slowing but does not typically show the periodic sharp wave complexes characteristic of sCJD.[12]
MRI- Although the results of brain magnetic resonance imaging (MRI) are neither sensitive or specific, they can reveal regions of reduced T2 signal in the midbrain and striatum in some individuals, as well as nonspecific cerebellar and/or cortical atrophy on structural neuroimaging [154]. Patients with GSS seldom show hyperintensity on diffusion-weighted imaging (DWI) and/or fluid-attenuated inversion recovery (FLAIR) sequences in the cortical ribbon and/or basal ganglia, which is a typical finding in sCJD. [13]
Gerstmann-Sträussler-Scheinker syndrome management
There isn't a particular GSS therapy that has been demonstrated to enhance results. In general, management is encouraging.
Two GSS patients who participated in an observational research utilizing intraventricular pentosan polysulfate may have had longer survival; however, this finding may not have therapeutic importance because prolonged longevity has also been noted in individuals who are not receiving treatment.[14]
References
- ↑ Hsiao K. "Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome". PMID 2564168.
- ↑ 2.0 2.1 Kretzschmar HA. "Prion protein mutation at codon 102 in an Italian family with Gerstmann-Sträussler-Scheinker syndrome". PMID 1348851. Check
|pmid=value (help). - ↑ Guiroy DC. "elationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, Creutzfeldt-Jakob disease and Gerstmann-Sträussler syndrome". PMID 8059606. Check
|pmid=value (help). - ↑ Brown P. "Clinical and molecular genetic study of a large German kindred with Gerstmann-Sträussler-Scheinker syndrome. Neurology". PMID 1672447. Check
|pmid=value (help). - ↑ Ghetti B. "Gerstmann-Sträussler-Scheinker disease and the Indiana kindred. Brain Pathol. Neurology". PMID 7767492. Check
|pmid=value (help). - ↑ Johnson RT. "Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. Brain Pathol. Neurology". PMID 9869672. Check
|pmid=value (help). - ↑ Arata H. "Early clinical signs and imaging findings in Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu). Brain Pathol. Neurology". PMID 16769939.. Check
|pmid=value (help). - ↑ Webb TE. "Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series. Brain Pathol. Neurology". PMID 18757886. Check
|pmid=value (help). - ↑ Barbanti P. "Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Sträussler-Scheinker disease. Brain Pathol. Neurology". PMID 8797472. Check
|pmid=value (help). - ↑ Barbanti P. "Gerstmann-Sträussler-Scheinker disease. Brain Pathol. Neurology". PMID 22411239. Check
|pmid=value (help). - ↑ Uflacker A. "Preimplantation genetic diagnosis (PGD) for genetic prion disorder due to F198S mutation in the PRNP gene. Brain Pathol. Neurology". PMID 24493558. Check
|pmid=value (help). - ↑ Franceschini A. "High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions. Brain Pathol. Neurology". PMID 28878311. Check
|pmid=value (help). - ↑ Wimberger D. "Gerstmann-Sträussler-Scheinker syndrome: MR findings.. Brain Pathol. Neurology". PMID 8454765. Check
|pmid=value (help). - ↑ Bone I. "Intraventricular pentosan polysulphate in human prion diseases: an observational study in the UK. Eur J Brain Pathol. Neurology". PMID 18355301. Check
|pmid=value (help).