Clinical Guidance
VPS35-related Parkinson disease (PARK-VPS35) is indistinguishable from Parkinson disease of unknown cause representing a simplex case (also referred to as "sporadic" Parkinson disease; see ). PARK-VPS35 is characterized by cardinal manifestations of typical parkinsonism (resting tremor, bradykinesia, rigidity, disturbance of postural reflexes). Similar to simplex Parkinson disease of unknown cause, non-motor symptoms also occur; however, neuropsychiatric disturbances and dementia are less common. Atypical features are also of lower frequency compared to simplex Parkinson disease of unknown cause. Disturbances of postural reflexes, autonomic manifestations, and sleep disorders occur at a similar rate to simplex Parkinson disease of unknown cause. PARK-VPS35 manifestations may be variable among affected individuals within the same family. To date, approximately 150 individuals with PARK-VPS35 have been identified [; ; ; ; ; ; ; ; ; ; Dulski et al, unpublished data]. Table 2. Select Features of VPS35-Related Parkinson Disease
Feature | % of Persons w/Feature1 | Comment |
|---|
Resting tremor | 98% | — |
Bradykinesia | 96% | — |
Rigidity | 95% | — |
Disturbance of postural reflexes | 67% | — |
Neuropsychiatric manifestations | 68% | — |
Cognitive issues | 42% | Learning difficulties, mild cognitive impairment, dementia |
Good response to levodopa | 80% | — |
Motor fluctuations | 85% | — |
Dyskinesia | 80% | — |
Dystonia | 32% | — |
Autonomic manifestations | 75% | Age of onset. Median age of onset was 52 years (interquartile range [IQR]: 45-61) in a group of 67 affected individuals , and 48 years (IQR: 44-56) in a group of 23 affected individuals . Parkinson subtype. The motor manifestations do not differ from simplex Parkinson disease of unknown cause. |
Source: GeneReviews — "VPS35-Related Parkinson Disease"
