Atypical frontotemporal dementia as a new clinical phenotype of Gerstmann-Straussler-Scheinker disease with the PrP-P102L mutation. Description of a previously unreported Italian family

Anna Rita Giovagnoli, Giuseppe Di Fede, Anna Aresi, Fabiola Reati, Giacomina Rossi, Fabrizio Tagliavini

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objective: To describe a new dementia phenotype of Gerstmann-Straussler-Scheinker disease (GSS) in a previously unreported Italian family. Design: Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), single positron emission tomography (SPECT) and molecular genetic studies. Setting: Neuropsychology Laboratory, and Division of Neuropathology and Neurology, "C. Besta" National Neurological Institute. Patients and participants: Three members of the family. Measurements and results: Standardised neuropsychological tests were used to determine cognitive patterns. The proband had a history of primary dementia characterised by loss of initiative, planning, behaviour control, awareness, language and memory; the two relatives suffered from progressive ataxia. MRI of the demented patient revealed brain atrophy with a hyperintense signal in the frontal cortex; SPECT revealed decreased perfusion in the left temporal and parietal cortex and left thalamus. The two ataxic patients showed cerebellar atrophy with no signs of altered perfusion. Analysis of the PRNP gene showed a proline/leucine substitution at codon 102 in all three patients, associated with methionine/valine heterozygosity at the polymorphic codon 129. Conclusions: Primary dementia with prominent frontotemporal signs is a new phenotypical expression of P102L-related GSS that coexists in the same family with the ataxic form of the disease. This remarkable variability suggests that still unidentified genetic or acquired factors may modulate the manifestations of GSS. Genetic examination of the PRNP should be included in the diagnostic work-up of patients with poorly classifiable dementia.

Original languageEnglish
Pages (from-to)405-410
Number of pages6
JournalNeurological Sciences
Volume29
Issue number6
DOIs
Publication statusPublished - 2008

Fingerprint

Gerstmann-Straussler-Scheinker Disease
Frontotemporal Dementia
Dementia
Phenotype
Mutation
Single-Photon Emission-Computed Tomography
Codon
Atrophy
Perfusion
Magnetic Resonance Imaging
Neuropsychology
Parietal Lobe
Behavior Control
Neuropsychological Tests
Valine
Frontal Lobe
Temporal Lobe
Ataxia
Neurology
Thalamus

Keywords

  • Dementia
  • Genetics
  • Gerstmann-Straussler-Sheinker disease
  • Neuropsychology

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

@article{d365708205de4609af783861265aabb7,
title = "Atypical frontotemporal dementia as a new clinical phenotype of Gerstmann-Straussler-Scheinker disease with the PrP-P102L mutation. Description of a previously unreported Italian family",
abstract = "Objective: To describe a new dementia phenotype of Gerstmann-Straussler-Scheinker disease (GSS) in a previously unreported Italian family. Design: Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), single positron emission tomography (SPECT) and molecular genetic studies. Setting: Neuropsychology Laboratory, and Division of Neuropathology and Neurology, {"}C. Besta{"} National Neurological Institute. Patients and participants: Three members of the family. Measurements and results: Standardised neuropsychological tests were used to determine cognitive patterns. The proband had a history of primary dementia characterised by loss of initiative, planning, behaviour control, awareness, language and memory; the two relatives suffered from progressive ataxia. MRI of the demented patient revealed brain atrophy with a hyperintense signal in the frontal cortex; SPECT revealed decreased perfusion in the left temporal and parietal cortex and left thalamus. The two ataxic patients showed cerebellar atrophy with no signs of altered perfusion. Analysis of the PRNP gene showed a proline/leucine substitution at codon 102 in all three patients, associated with methionine/valine heterozygosity at the polymorphic codon 129. Conclusions: Primary dementia with prominent frontotemporal signs is a new phenotypical expression of P102L-related GSS that coexists in the same family with the ataxic form of the disease. This remarkable variability suggests that still unidentified genetic or acquired factors may modulate the manifestations of GSS. Genetic examination of the PRNP should be included in the diagnostic work-up of patients with poorly classifiable dementia.",
keywords = "Dementia, Genetics, Gerstmann-Straussler-Sheinker disease, Neuropsychology",
author = "Giovagnoli, {Anna Rita} and {Di Fede}, Giuseppe and Anna Aresi and Fabiola Reati and Giacomina Rossi and Fabrizio Tagliavini",
year = "2008",
doi = "10.1007/s10072-008-1025-z",
language = "English",
volume = "29",
pages = "405--410",
journal = "Neurological Sciences",
issn = "1590-1874",
publisher = "Springer-Verlag Italia s.r.l.",
number = "6",

}

TY - JOUR

T1 - Atypical frontotemporal dementia as a new clinical phenotype of Gerstmann-Straussler-Scheinker disease with the PrP-P102L mutation. Description of a previously unreported Italian family

AU - Giovagnoli, Anna Rita

AU - Di Fede, Giuseppe

AU - Aresi, Anna

AU - Reati, Fabiola

AU - Rossi, Giacomina

AU - Tagliavini, Fabrizio

PY - 2008

Y1 - 2008

N2 - Objective: To describe a new dementia phenotype of Gerstmann-Straussler-Scheinker disease (GSS) in a previously unreported Italian family. Design: Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), single positron emission tomography (SPECT) and molecular genetic studies. Setting: Neuropsychology Laboratory, and Division of Neuropathology and Neurology, "C. Besta" National Neurological Institute. Patients and participants: Three members of the family. Measurements and results: Standardised neuropsychological tests were used to determine cognitive patterns. The proband had a history of primary dementia characterised by loss of initiative, planning, behaviour control, awareness, language and memory; the two relatives suffered from progressive ataxia. MRI of the demented patient revealed brain atrophy with a hyperintense signal in the frontal cortex; SPECT revealed decreased perfusion in the left temporal and parietal cortex and left thalamus. The two ataxic patients showed cerebellar atrophy with no signs of altered perfusion. Analysis of the PRNP gene showed a proline/leucine substitution at codon 102 in all three patients, associated with methionine/valine heterozygosity at the polymorphic codon 129. Conclusions: Primary dementia with prominent frontotemporal signs is a new phenotypical expression of P102L-related GSS that coexists in the same family with the ataxic form of the disease. This remarkable variability suggests that still unidentified genetic or acquired factors may modulate the manifestations of GSS. Genetic examination of the PRNP should be included in the diagnostic work-up of patients with poorly classifiable dementia.

AB - Objective: To describe a new dementia phenotype of Gerstmann-Straussler-Scheinker disease (GSS) in a previously unreported Italian family. Design: Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), single positron emission tomography (SPECT) and molecular genetic studies. Setting: Neuropsychology Laboratory, and Division of Neuropathology and Neurology, "C. Besta" National Neurological Institute. Patients and participants: Three members of the family. Measurements and results: Standardised neuropsychological tests were used to determine cognitive patterns. The proband had a history of primary dementia characterised by loss of initiative, planning, behaviour control, awareness, language and memory; the two relatives suffered from progressive ataxia. MRI of the demented patient revealed brain atrophy with a hyperintense signal in the frontal cortex; SPECT revealed decreased perfusion in the left temporal and parietal cortex and left thalamus. The two ataxic patients showed cerebellar atrophy with no signs of altered perfusion. Analysis of the PRNP gene showed a proline/leucine substitution at codon 102 in all three patients, associated with methionine/valine heterozygosity at the polymorphic codon 129. Conclusions: Primary dementia with prominent frontotemporal signs is a new phenotypical expression of P102L-related GSS that coexists in the same family with the ataxic form of the disease. This remarkable variability suggests that still unidentified genetic or acquired factors may modulate the manifestations of GSS. Genetic examination of the PRNP should be included in the diagnostic work-up of patients with poorly classifiable dementia.

KW - Dementia

KW - Genetics

KW - Gerstmann-Straussler-Sheinker disease

KW - Neuropsychology

UR - http://www.scopus.com/inward/record.url?scp=58149088848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149088848&partnerID=8YFLogxK

U2 - 10.1007/s10072-008-1025-z

DO - 10.1007/s10072-008-1025-z

M3 - Article

C2 - 19030774

AN - SCOPUS:58149088848

VL - 29

SP - 405

EP - 410

JO - Neurological Sciences

JF - Neurological Sciences

SN - 1590-1874

IS - 6

ER -