Résumé
Parkinsonism and Related Disorders, Elsevier, 2020, 80, pp.73-81 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 .