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Isolated parkinsonism is an atypical presentation of GRN and C9orf72 gene mutations Authors
- Source :
- Parkinsonism and Related Disorders, Parkinsonism and Related Disorders, Elsevier, 2020, 80, pp.73-81. ⟨10.1016/j.parkreldis.2020.09.019⟩, Parkinsonism & Related Disorders, Parkinsonism & Related Disorders, 2020, 80, pp.73-81. ⟨10.1016/j.parkreldis.2020.09.019⟩
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- Introduction A phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It still remains controversial if this association is fortuitous or not, and which clinical clues could reliably suggest a genetic FTD etiology in IPD patients. This study aims to describe the clinical characteristics of FTD mutation carriers presenting with IPD phenotype, provide neuropathological evidence of the mutation's causality, and specifically address their “red flags” according to current IPD criteria. Methods Seven GRN and C9orf72 carriers with isolated parkinsonism at onset, and three patients from the literature were included in this study. To allow better delineation of their phenotype, the presence of supportive, exclusion and “red flag” features from MDS criteria were analyzed for each case. Results Amongst the ten patients (5 GRN, 5 C9orf72), seven fulfilled probable IPD criteria during all the disease course, while behavioral/language or motoneuron dysfunctions occurred later in three. Disease duration was longer and dopa-responsiveness was more sustained in C9orf72 than in GRN carriers. Subtle motor features, cognitive/behavioral changes, family history of dementia/ALS were suggestive clues for a genetic diagnosis. Importantly, neuropathological examination in one patient revealed typical TDP-43-inclusions without alpha-synucleinopathy, thus demonstrating the causal link between FTD mutations, TDP-43-pathology and PD phenotype. Conclusion We showed that, altogether, family history of early-onset dementia/ALS, the presence of cognitive/behavioral dysfunction and subtle motor characteristics are atypical features frequently present in the parkinsonian presentations of GRN and C9orf72 mutations.
- Subjects :
- Male
0301 basic medicine
Parkinson's disease
TDP-43
Disease
Bioinformatics
Progranulins
0302 clinical medicine
C9orf72
Age of Onset
Family history
PSP
Parkinsonism
Parkinson Disease
FTD
Middle Aged
Pedigree
3. Good health
Neurology
Frontotemporal Dementia
Neurons and Cognition (q-bio.NC)
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
FTLD
GRN
Frontotemporal dementia
CBS
03 medical and health sciences
Parkinsonian Disorders
medicine
Humans
Dementia
Cognitive Dysfunction
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Aged
C9orf72 Protein
business.industry
medicine.disease
nervous system diseases
030104 developmental biology
Quantitative Biology - Neurons and Cognition
FOS: Biological sciences
Mutation
Etiology
Neurology (clinical)
Geriatrics and Gerontology
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 13538020 and 18735126
- Database :
- OpenAIRE
- Journal :
- Parkinsonism and Related Disorders, Parkinsonism and Related Disorders, Elsevier, 2020, 80, pp.73-81. ⟨10.1016/j.parkreldis.2020.09.019⟩, Parkinsonism & Related Disorders, Parkinsonism & Related Disorders, 2020, 80, pp.73-81. ⟨10.1016/j.parkreldis.2020.09.019⟩
- Accession number :
- edsair.doi.dedup.....2ca2b5083565bb59e5ff8924b5843c07