Τίτλος:
Frontotemporal dementia as the presenting phenotype of p.A53T mutation carriers in the alpha-synuclein gene
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction The p.A53T point mutation in SNCA, the alpha-synuclein gene, has been linked to a rare dominant form of Parkinson's disease (PD). Methods Here, we describe two apparently unrelated cases of p.A53T (G209A) SNCA mutation carriers with an atypical initial manifestation and disease course. Moreover, cerebrospinal fluid (CSF) levels of tau, p-tau and amyloid Aβ42 were measured in these patients and in an additional cohort of 5 symptomatic and 2 asymptomatic p.A53T carriers without an initial manifestation of dementia. Results Both patients exhibited an early onset frontal-dysexecutive dysfunction with apathy and emotional blunting resembling frontotemporal dementia (FTD). Motor symptoms typical of Parkinson's disease appeared only later in the disease course and were less prominent than cognitive ones, which included language impairment. Autonomic dysfunction and myoclonus also emerged in a more advanced disease stage. In both patients, Brain Magnetic Resonance Imaging showed fronto-temporo-parietal atrophy, and CSF analysis showed elevated tau protein levels. In contrast, tau protein levels were normal in a cohort of 7 other p.A53T mutation carriers (5 symptomatic/2 asymptomatic). A screen of Greek patients presenting with frontotemporal dementia failed to identify any additional subjects with the p.A53T SNCA mutation. Conclusion Although cognitive decline has been recognized as a feature of the full-blown clinical picture of p.A53T related parkinsonism, a predominant frontotemporal dementia-like phenotype at presentation has not been previously described. This may represent a subtype of this disorder, with distinctive clinical, imaging and CSF biochemical characteristics, in which additional genetic or epigenetic factors may play a role. © 2016 Elsevier Ltd
Συγγραφείς:
Bougea, A.
Koros, C.
Stamelou, M.
Simitsi, A.
Papagiannakis, N.
Antonelou, R.
Papadimitriou, D.
Breza, M.
Tasios, K.
Fragkiadaki, S.
Geronicola Trapali, X.
Bourbouli, M.
Koutsis, G.
Papageorgiou, S.G.
Kapaki, E.
Paraskevas, G.P.
Stefanis, L.
Περιοδικό:
Parkinsonism and Related Disorders
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
alpha synuclein; amyloid beta protein[1-42]; donepezil; levodopa; progranulin; tau protein; alpha synuclein, adult; anxiety; apathy; Article; autonomic dysfunction; case report; cerebrospinal fluid analysis; clinical feature; cohort analysis; daily life activity; dementia; disease course; disease severity; epigenetics; euphoria; frontotemporal dementia; gene mutation; genetic screening; human; male; middle aged; Mini Mental State Examination; myoclonus; neuropsychological test; nuclear magnetic resonance imaging; parkinsonism; phenotype; point mutation; protein cerebrospinal fluid level; short term memory; SNCA gene; Unified Parkinson Disease Rating Scale; urinary urgency; diagnostic imaging; frontotemporal dementia; genetics; heterozygote; missense mutation; pedigree; phenotype, Adult; alpha-Synuclein; Frontotemporal Dementia; Heterozygote; Humans; Male; Middle Aged; Mutation, Missense; Pedigree; Phenotype
DOI:
10.1016/j.parkreldis.2016.12.002
