Parkinson's Disease, Atypical
Genetic atypical Parkinson's disease (PD) describes forms of PD that resemble the common PD, but feature prominent atypical clinical signs and symptoms that can be sub-grouped into atypical monogenic forms caused by mutations in 1) the ATP13A2, DNAJC6, FBXO7, SYNJ1, VPS13C, and DCTN genes; 2) monogenic PD more closely resembling common PD, but associated with atypical features in at least a subset of cases (SNCA-, LRRK2-, VPS35-, Parkin-, PINK1-, and DJ-1-linked PD; 3) carriers of mutations in genes that are usually associated with other movement disorders but may present with parkinsonism, such as dopa-responsive dystonia. Overall an early age at onset is a feature of the so called atypical, genetically determined PD.
Early cognitive decline is present in carriers of mutations across several different genes. Several clinical features can serve as red flags for specific forms of atypical PD including a supranuclear gaze palsy in ATP13A2 mutation carriers or hypoventilation linked to mutations in the DCTN1 gene.
From Weisbach 2019.
The International Parkinson's Disease and Movement Disorder Society Gene Database (MDSGene) initiative has been launched in 2016 and grown to become a large international project.
MDSGene currently contains >1150 variants described in ∼5700 movement disorder patients in almost 1000 publications including monogenic forms of PD clinically resembling idiopathic (PARK-PINK1, PARK-Parkin, PARK-DJ-1, PARK-SNCA, PARK-VPS35, PARK-LRRK2), as well as of atypical PD (PARK-SYNJ1, PARK-DNAJC6, PARK-ATP13A2, PARK-FBXO7).
From Klein 2018