Page 210 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 8
biomarkers 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.47
Late-onset disorders in 22q11.2DS and other GNDs; potential (shared)
underlying mechanisms
In 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
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