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Chapter 3124Research implicationsAlthough genetic variants have been found to explain only a small portion of PD,28, 29 identification of these genes has contributed to the understanding of PD pathophysiology. For example, studies of duplications and triplications of SNCA, encoding for alpha-synuclein, provided evidence for the relation between gene dosage and severity of parkinsonian features.30 Although 22q11.2DS has been reported most related to PD, other genetic neurodevelopmental disorders have been associated with neurodegenerative parkinsonism as well, and several shared underlying mechanisms related to the neurodevelopmental disorder and PD have been proposed.31 Research of the influence of genetic variants on PD risk and disease trajectory are crucial for the identification of novel treatment strategies that may prevent or slow down disease progression. Since 22q11.2DS and other genetic neurodevelopmental disorders are often identified at an early age, long-term follow up of asymptomatic/presymptomatic individuals may generate knowledge of contributors to the development of PD and the ability of (environmental) factors to delay or slow down PD. Studies may include evaluation of parkinsonian symptoms using the Unified Parkinson’s Disease Rating Scale, prodromal features such as RMD using polysomnography, and questionnaires for the study of environmental factors such as diet and exercise. Results may help to improve counseling of individuals at risk of developing PD. Furthermore, identification of genetic variants such as 22q11.2DS, that are associated with an increased risk of PD, facilitates the use of cell and animal models, 32, 33 that may help to identify disease-modifying agents for adults with 22q11.2DS and PD which may also be of relevance to the general population.Strengths and limitationsStrengths include the large study sample of adults with a, relatively rare, diagnosis of 22q11.2DS and recruitment from different sites, covering different regions and organizations. An important limitation includes the retrospective study design. Under-recognition of PD prevalence may be related to clinical notes that may have lacked relevant information regarding a PD diagnosis and the fact that most adults were not screened for PD. In addition, adults may have had difficulties with signalizing symptoms of PD and/or seeking help.5 Since genetic testing in adults with an intellectual