The Movement Disorder Society’s Genetic Mutation Database Systematic Review focuses on monogenic atypical parkinsonism induced by mutations in the genes ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C. From 77 articles, researchers examined 673 citations and retrieved genotypic and phenotypic data for 140 patients (73 families). Researchers used an ensemble of bootstrap-aggregated (“bagged”) decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95% CI, 86.3% –86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased bodyweight, minimyoclonus, vertical gaze palsy, autonomic symptoms, nonmotor symptoms, levodopa response quantification, and cognitive decline.
When 2063 data sets from the Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations were compared to patients with monogenic typical parkinsonism, the age at onset was younger in monogenic atypical parkinsonism (24 vs. 40 years; P = 1.2647 x 10-12) and the levodopa response was less favorable (49% vs. 93%). In addition, they included data from 362 individuals with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration to compare monogenic and non-monogenic atypical parkinsonism. Although they share many clinical features with monogenic atypical forms, their later median age at onset (64 years; IQR, 57–70 years) is typically enough to distinguish them.
Finally, in atypical types of parkinsonism, age at onset, the existence of particular manifestations, and degree of levodopa response influence differential diagnostic considerations and genetic testing recommendations. The Authors, 2021 Wiley Periodicals LLC publishes Movement Disorders on behalf of the International Parkinson Movement Disorder Society.
Reference:movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28517
