Page 124 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 3
is a male predominance of PD, and motor symptoms usually start at an
earlier age compared to females.8 One possible explanation may be that
other factors than sex, such as genetic susceptibility, are more dominant
in 22q11.2DS.10 Speculatively, another explanation may be related to
hemizygosity of COMT, a gene located within the typically deleted 22q11.2
region and encoding for the enzyme (catechol-O-methyltransferase)
important for degradation of catecholamines, that may result in dopamine
autotoxicity.11 COMT expression is inhibited by estrogen, resulting in lower
COMT activity in females than in males, which may lead to increased
dopamine levels,12 and autotoxicity, resulting in a higher vulnerability to
develop PD. Our results showing an increase in PD prevalence in males
aged 50 years and older but a decrease in females, may also be explained
by changes in estrogen levels in females before and after menopause.
A separate category of adults with suspected PD was included to account for
the fact that there were several adults with a clinical suspicion of PD, although
not meeting all criteria for PD. Limiting results to adults with a formal diagnosis
of PD would most likely result in an underestimation of PD prevalence
in 22q11.2DS. In case adults with a suspicion of PD were included in our
analysis, it was found that PD estimates almost doubled (3.4%). Although
hallmark features of PD in the general population were found in adults with
22q11.2DS,2, 4 there may be several reasons for clinicians to be hesitant to
diagnose PD in adults with 22q11.2DS. Adults with 22q11.2DS often have a
complex neuropsychiatric presentation, with additional movement disorders
such as dystonia and catatonia, 13, 14 and/or psychiatric disorders such as
psychosis and (a history of) medication-induced parkinsonism,15 that may
overshadow and/or complicate recognition of parkinsonian features. The
atypical early age of motor onset may further increase the likelihood of
parkinsonian symptoms to be attributed to other conditions associated
with 22q11.2DS. In addition, clinicians may be hesitant with referring to
a neurologist because of the added burden of hospital visits, follow-up
examinations or doubt about potential benefits.
Clinical implications
In individuals with 22q11.2DS under the age of 40 years, clinicians should be
aware of the possibility of PD. Motor examination, preferably by a movement
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