Characterization of Movement Disorder Phenomenology in Genetically Proven, Familial Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis.
BACKGROUND
Mutations in granulin (PGRN) and tau (MAPT), and hexanucleotide repeat expansions near the C9orf72 genes are the most prevalent genetic causes of frontotemporal lobar degeneration. Although behavior, language and movement presentations are common, the relationship between genetic subgroup and movement disorder phenomenology is unclear.


OBJECTIVE
We conducted a systematic review and meta-analysis of the literature characterizing the spectrum and prevalence of movement disorders in genetic frontotemporal lobar degeneration.


METHODS
Electronic databases were searched using terms related to frontotemporal lobar degeneration and movement disorders. Articles were included when cases had a proven genetic cause. Study-specific prevalence estimates for clinical features were transformed using Freeman-Tukey arcsine transformation, allowing for pooled estimates of prevalence to be generated using random-effects models.


RESULTS
The mean age at onset was earlier in those with MAPT mutations compared to PGRN (p<0.001) and C9orf72 (p = 0.024). 66.5% of subjects had an initial non-movement presentation that was most likely a behavioral syndrome (35.7%). At any point during the disease, parkinsonism was the most common movement syndrome reported in 79.8% followed by progressive supranuclear palsy (PSPS) and corticobasal (CBS) syndromes in 12.2% and 10.7%, respectively. The prevalence of movement disorder as initial presentation was higher in MAPT subjects (35.8%) compared to PGRN subjects (10.1). In those with a non-movement presentation, language disorder was more common in PGRN subjects (18.7%) compared to MAPT subjects (5.4%).


CONCLUSIONS
This represents the first systematic review and meta-analysis of the occurrence of movement disorder phenomenology in genetic frontotemporal lobar degeneration. Standardized prospective collection of clinical information in conjunction with genetic characterization will be crucial for accurate clinico-genetic correlation.
The Morton and ‎Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, TWH, Toronto, Canada.|Department of Medicine, Division of Neurology, University of Toronto, Toronto, Canada.|Centro integral en Neurociencias A.C. (CINAC)/HM Hospitales- Puerta del Sur, CEU-San Pablo University, Madrid, Spain.
Carmen
C
Gasca-Salas
Centro integral en Neurociencias A.C. (CINAC)/HM Hospitales- Puerta del Sur, CEU-San Pablo University, Madrid, Spain.|Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre, Toronto, Canada.
Mario
M
Masellis
Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Edwin
E
Khoo
Department of Neurology, University of Virginia, Charlottesville, Virginia, United States of America.
Binit B
BB
Shah
Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
David
D
Fisman
The Morton and ‎Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, TWH, Toronto, Canada.
Anthony E
AE
Lang
Department of Medicine, Division of Neurology, University of Toronto, Toronto, Canada.|Jeff and Diane Ross Movement Disorders Clinic, Baycrest Center for Geriatric Health, Toronto, Canada.
Galit
G
Kleiner-Fisman
D017668:Age of Onset; D057174:Frontotemporal Lobar Degeneration / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D009069:Movement Disorders / Q000209:etiology* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D000077153:Progranulins; D016875:tau Proteins / Q000235:genetics*
D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D016875:tau Proteins