Page 187 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

The eye as a window to the brain
and that lies within the distal region of the typical 22q11.2 deletion, i.e.,
within LCR22C-LCR22D, is SNAP29 (synaptosome associated protein 29).44
This gene encodes a protein involved in several membrane trafficking
steps, and is present in protein complexes that play a role in the subretinal
neovascularization of age-related macular degeneration.45, 46 Mice with
a loss of function mutation of Snap29 have shown significant thinning of
the inner and outer nuclear layers of the retina.47 In addition, excessive
mitophagy, responsible for removal of damaged mitochondria, has been
suggested to play a role in retinal ganglion cell neurodegeneration.48 This is of
interest, since it has also been hypothesized that mitochondrial dysfunction
plays an important role in neurodegenerative processes in individuals with
22q11.2DS.49, 50 Thus, the apparent decrease in RNFL (that is formed by
axons of ganglion cells) with age in 22q11.2DS, and not in controls, may
be indicative of increased mitochondrial dysfunction and axonal damage
and may therefore be a potential biomarker for early neurodegeneration in
22q11.2DS. Vascularization of the central nervous system may play a role,
but has been scarcely studied in 22q11.2DS. Findings of the few studies
include hypoplastic and smaller cerebral arteries,51 thicker cortical veins
in patients with migrational disorders (e.g., polymicrogyria), and smaller
veins of abnormal number or disorganized appearance.52 Research has
also shown elevated cerebral blood flow in the left and right putamen, the
right fusiform gyrus, and the left middle temporal gyrus in 22q11.2DS,
overlapping with regions of elevated blood flow in patients with idiopathic
schizophrenia.53 Increased cerebral blood flow has been found to be
positively associated with retinal vascular FD in a cohort of healthy adults
aged 65 years and over.54 Another factor that may relate to retinovascular
and retinoneural abnormalities is cyanotic congenital heart disease, through
a complex interplay of factors including hypoxemia.55
Strengths and limitations
The study provides the first systematic quantitative assessment of retinal
morphological features in 22q11.2DS, in a relatively large study sample
for a rare disorder. Retinal vascular parameters and retinal layer thickness
were assessed using (semi-)automated software, minimizing interrater
differences. Limitations of the study include the cross-sectional design and
young average age of the study sample. Future longitudinal studies are
needed to study changes in retinal vascular parameters and RNFL thickness
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