Page 212 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 8
chapter 6, has also been reported in individuals from the general population
but only after the age of 65 years.43 These examples may suggest that
some of the mechanisms contributing to age-related disorders are similar
between adults with 22q11.2DS and the general population, but have their
onset earlier in life. These findings may also suggest the presence of other
neurodegenerative conditions in GNDs at an earlier age than would be
expected based on results from the general population. In future research it
would be interesting to study other neurodegenerative conditions in GNDs,
such as cognitive decline/dementia.
With respect to 22q11.2DS, hemizygosity of protein-coding genes within
the 22q11.2 deletion region that were suggested to contribute to conditions
at adult age included TBX1 and genes involved in mitochondrial function.54
TBX1 is important for the 22q11.2DS somatic phenotype, and is involved
in the development of the cardiac and vascular system, including the stria
vascularis, central nervous system and inner ear, including the semicircular
canal. 55, 56 Described in chapter 4, hemizygosity of TBX1 may result in
vulnerability of the cochlea and contribute to age-related hearing loss. In
addition, TBX1 may be responsible for retinovascular abnormalities found in
individuals with 22q11.2DS because of its involvement in angiogenesis and
vessel branching described in chapter 6.
57 Other candidate genes include
those involved in mitochondrial function; at least six are located in the
22q11.2 region.54 Mitochondrial dysfunction and oxidative stress have been
proposed, in chapters 3, 4 and 6, as possible contributors to degenerative
changes which may contribute to the development of age-related hearing
loss, retinal abnormalities, Parkinson’s disease as well as other conditions
outside the scope of this thesis but important for the adult phenotype, such
as schizophrenia. 58-61
Methodological considerations
Results described in this thesis should be considered in the context of
several strengths and limitations. Some related to more than one study
and will be discussed in the following paragraphs because they may be of
relevance to future studies. Strengths included the relatively large samples
of adults with 22q11.2DS. In addition, adults were often examined as part
of routine 22q11.2DS-related care.62 For example, ophthalmic, neurologic
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