Page 16 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 1
that is important for catecholamine degradation, including dopamine, and
PRODH for proline degradation.22 Some evidence, from mice and human
studies, indicate a role for COMT and PRODH in the development of the
neuropsychiatric phenotype of 22q11.2DS.22-24 In addition, mitochondrial
dysfunction, resulting from deletion of at least six mitochondrial genes
in the 22q11.2 region,25 may play a role in the cardiac, endocrinologic,
neurologic and psychiatric phenotype of 22q11.2DS.23, 25-27 DGCR8 was
found to be involved in the development of the cardiac, immune and central
nervous system,28 and in the biogenesis of mircoRNAs.29 Non-coding
regulatory genes such as microRNAs may be important for the etiology of
22q11.2DS, and have been implicated in fundamental cellular processes
such as proliferation and apoptosis.21, 30
Figure 2. 22q11.2 deletion region and genes located in this region (Zinkstok et al.,23 reproduced
from Guna et al.31)
Adults with 22q11.2 deletion syndrome
Research in adults with 22q11.2DS is important because studies in
adults are much more scarce compared to studies in children, and
manifestations differ from those in children.32, 33 Differences include, for
example, an increased risk of developing certain psychiatric disorders
such as schizophrenia at adolescent and adult age, 32 whereas in children
the emphasis is on the detection and treatment of congenital anomalies
and developmental disabilities.34 In order to improve genetic counseling
and treatment for adults with 22q11.2DS, it is important to have a good
understanding of the natural history, including prevalence estimates of
conditions associated with the adult phenotype.35 In addition, knowledge
of the influence of age, sex or co-morbidities may facilitate personalized
screening and treatment in subgroups that are at increased risk of a certain
condition and may prevent overly screening in those who are not. Clinically
relevant features at adult age include, but are not limited to, impairments
in cognitive and adaptive functioning, anxiety and psychotic disorders,
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