Page 234 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Appendix l
genetic testing. Further recognition of parkinsonism in these GNDs may
provide insights into the mechanisms causing parkinsonism in the general
population, crucial for the development of disease-modifying treatments.
In chapter 3 the estimated prevalence of Parkinson’s disease is examined
in adults with 22q11.2DS. An increased risk of Parkinson’s disease, of 20-to-
70-fold, has previously been suggested in adults with 22q11.2DS. However,
prevalence estimates were based on only 68 individuals with 22q11.2DS, at
a relatively young age of 35 to 64 years. A multicenter cross-sectional study
was conducted that included 856 adults (47% male, at mean age 46.5 ± 15.4
years) with 22q11.2DS who visited one of the specialized 22q11.2DS clinics
in the Netherlands (Maastricht University Medical Centre and ‘s Heeren Loo),
Belgium (University Hospital Leuven), Canada (Dalglish Family 22q Clinic,
Toronto) and Chile (University of Santiago). Parkinson’s disease was defined
as a clinical diagnosis by a neurologist, and presence of bradykinesia and at
least one of either rest tremor or rigidity. Suspected Parkinson’s disease was
defined as a clinical diagnosis of Parkinson’s disease or a clinical suspicion
of Parkinson’s disease without complying to the formal criteria. The results
indicate a prevalence of 1.8% for Parkinson’s disease (95% CI: 0.9 – 2.6) and
3.4% (95% CI: 2.2 – 4.6%) in case adults suspected of Parkinson’s disease
were included. A sharp increase in the prevalence of Parkinson’s disease
was seen in adults with 22q11.2DS aged 50 years and older (11.7%). In
contrast to Parkinson’s disease in the general population, male sex was
not associated with an increased risk in adults with 22q11.2DS. Based on
these findings, periodic evaluation of motor symptoms by a neurologist,
preferably a movement disorder specialist, seems justified in adults with
22q11.2DS aged 40 years and older. Individuals with 22q11.2DS at any age
showing parkinsonian motor signs may benefit from careful monitoring
and referral for neurological examination in case of doubt of the etiology.
In chapter 4 results regarding hearing loss and otolaryngological
conditions in adults with 22q11.2DS are reported. Previous studies
showed an increased prevalence of hearing loss and chronic otitis media
in 22q11.2DS. Since most studies focused on children, and the knowledge
on adults is still scarce, the aim of this study was to report on hearing and
otolaryngological findings in adults. Therefore, a cross-sectional study was
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