Objective: We compared motor features in patients with familial frontotemporal dementia (f-FTD) and MAPT, GRN or C9orf72 gene mutations. Special emphasis was placed on the evaluation of parkinsonism.

Background: Little data exists on the differential occurrence of motor features including parkinsonism in patients with f-FTD due to different genetic mutations.

Method: Clinical data on motor features (frequency and severity) and demographic data was analysed in 84 patients with mutations in MAPT (n=31), GRN (n=20), and C9orf72 (n=31); 44 of these patients had motor signs. All patients participated in the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) study.

Results: Parkinsonian signs including resting tremor, hypokinesia and falls as well as spastic gait and impairment of vertical saccades were mostly encountered in the MAPT group. Dystonia was most severe and most frequent in the GRN group. Muscle atrophy was most severe in patients with the C9orf72 mutation (P<0.05). Age at onset (AAO) of motor features was lowest in patients with MAPT and highest in patients with C9orf72 mutations (median: 48 versus 67 years; P<0.0167). AAO of overall disease onset (as well as of cognitive and behavioral signs) was lowest in patients with MAPT mutations (P<0.0167).On the Unified Parkinson’s Disease Rating Scale (UPDRS) III, no statistical significant results were seen across groups. Progressive supranuclear palsy rating scale (PSPRS) total scores were highest in patients with GRN mutations (P=0.049, n=57). Several clinical phenotypes were associated only with mutations in one of the three genes. Phenotypes compatible with PSP and Parkinson's disease were seen only in individuals with MAPT mutations. A phenotype compatible with corticobasal syndrome occurred only in patients with GRN mutations.

Conclusion: Parkinsonism (resting tremor, hypokinesia and postural instability) and impaired saccades were most frequent and most severe in the patients with MAPT mutations. This group also had the earliest AAO of motor features. Differential severity of specific motor features and differential AAO for motor, cognitive and behavioral signs was found in f-FTD associated with MAPT, GRN or C9orf72 mutations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsonism-and-other-motor-features-in-familial-frontotemporal-dementia-with-mutations-in-the-mapt-grn-or-c9orf72-gene-lefftds-cohort/