Page 124 - Demo

Chapter 3122is 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 implicationsIn 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