Page 186 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 6
In 22q11.2DS, thinning of RNFL segments with increasing age are
consistent with findings of a study in adults in the general population.34 In
that study, retinal layer thinning increasing with age was mainly found in
the macular RNFL and the retinal ganglion cell layer. In Parkinson’s disease,
loss of retinal ganglion cells and axons has been found, with thinning of the
peripapillary RNFL in the inferotemporal segments,35 which is in line with
our findings in adults with 22q11.2DS.
Implications
Together, findings of this study, and considering the consistency with previous
studies in community-based schizophrenia spectrum and neurodegenerative
disorders,16, 20, 34, 35 suggest that retinal FD and tortuosity may be useful
biomarkers for psychotic disorders, and FD and RNFL thickness for (early)
neurodegenerative processes in 22q11.2DS. Similarly, it may aid in our
understanding of disease trajectories in other genetic neurodevelopmental
disorders.36 An example may be found in a study in adults with Down
syndrome that observed thinning of macular RNFL to be related to early
Alzheimer’s disease pathology.37 To account for the earlier discussed factors
that may contribute to retinal vessel morphology, and the medical complexity,
adequately powered longitudinal studies are needed to better understand the
changes that may occur within patients with 22q11.2DS.
Mechanisms underlying retinovascular and retinoneural abnormalities in
22q11.2DS
Potential biological mechanisms that may play a role in retinovascular
and retinoneural abnormalities in 22q11.2DS include genetic variants,
excessive mitophagy, cardiovascular abnormalities, and tissue oxygenation
changes.29, 38, 39 One candidate gene for retinal vascular abnormalities
that lies within the LCR22A-LCR22B region is TBX1, encoding a T-box
transcription factor. TBX1 is important for cardiovascular development and
regulates the vascular endothelial growth factor receptor 3-gene VEGFR3
in brain endothelial cells.40-42 Studies in mice have indicated an important
role for VEGFR3 in regulating angiogenesis and controlling branching of
blood vessels in the retina and hindbrain.43 Inactivation of tbx1 in mice has
shown to result in vascular abnormalities, impaired vascular functioning,
and insufficient oxygenation in affected brain regions.40 Another gene that
has been postulated to be involved in retinal abnormalities in 22q11.2DS,
184