Study Rationale: Inherited Parkinson-dystonia syndromes are rare but ideal models for studying genetically complex disorders, such as Parkinson’s disease (PD), as their underlying cause — mutation in a gene — is clearly defined. Interestingly, within the inherited syndromes in our study, there are individuals who carry the relevant mutation but who do not develop symptoms of the disorder. However, subtle changes in brain function or how different brain regions communicate can sometimes be detected in carriers that lack other, more easily observable clinical symptoms.
Hypothesis: We will assess the connection between sensory perception and motor actions in different subgroups of inherited Parkinson-dystonia syndromes and determine whether individuals who develop clinical symptoms differ from those who remain healthy despite carrying the same genetic mutation.
Study Design: Using a mobile testing unit, we will conduct home examinations of mutation carriers with and without symptoms for three different inherited Parkinson-dystonia syndromes. To detect even subtle changes, which the mutation carriers might not even notice in day-to-day life, we will use a detailed video-based and -documented movement examination along with a noninvasive magnetic stimulation technique that probes how a sensory input, such as electrical stimulation, can influence the motor response in a hand muscle.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our study will allow us to define specific markers that protect some mutation carriers from having clinical symptoms and to identify neurophysiological characteristics that all carriers share despite having different clinical presentations. This information will improve our understanding of these disorders and facilitate the development of new treatment strategies.
Next Steps for Development: Through our study, we will build up large groups of mutation carriers that have received an in-depth clinical and neurophysiological examination and can be investigated longitudinally in future studies. Our findings should also be applicable to individuals with genetically undefined Parkinson and dystonia syndromes.