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Chapter 8208biomarkers for psychiatric and (early) neurodegenerative disorders in individuals with 22q11.2DS. The ability to identify individuals with an increased risk may be further increased by combining multiple biomarkers, such as neurofilament light chain for neurodegenerative disorders.45 In addition, studying retinovascular and retinoneural parameters in other GNDs may aid in our understanding of disease trajectories,46 and may identify individuals at risk of other late-onset disorders such as Alzheimer’s disease in adults with Down syndrome.47Late-onset disorders in 22q11.2DS and other GNDs; potential (shared) underlying mechanismsIn the study described in chapter 3, it was found that adults with 22q11.2DS have a high prevalence of Parkinson’s disease,48 and in chapter 2 many other GNDs were found to be associated with neurodegenerative parkinsonism as well. Although no conclusions can be drawn regarding the prevalence of (neurodegenerative) parkinsonism in these GNDs, and under-recognition and under-study of parkinsonism in GNDs probably resulted in an incomplete list, the literature study in chapter 2 provides clues as to which GNDs may be more susceptible to (neurodegenerative) parkinsonism and raises awareness for parkinsonism in the group of GNDs as a whole. Findings of early-onset and progressive motor symptoms combined with neuronal loss in the majority of individuals with neuropathological results, were supportive of neurodegeneration in a substantial proportion of the included individuals. In addition, for several GNDs cellular mechanisms could be identified, including mitochondrial dysfunction, that may be involved in the pathophysiology of both developmental as well as neurodegenerative disorders (Figure 1). A genetic susceptibility to neurodegeneration may also include dysfunction of micro RNAs, that may alter the expression of multiple genes and provide the basis for neuronal cell deteriotion.49 Micro RNAs are important for cell regulation, development, differentiation, stress response and apoptosis, and age-related changes in expression have been found.49, 50 Several micro RNAs lie within the 22q11.2 deletion region, and were suggested to be important for the maturation of the adolescent and early adult brain.51