Page 126 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 3
Research implications
Although genetic variants have been found to explain only a small
portion of PD,28, 29 identification of these genes has contributed to the
understanding of PD pathophysiology. For example, studies of duplications
and triplications of SNCA, encoding for alpha-synuclein, provided evidence
for the relation between gene dosage and severity of parkinsonian
features.30 Although 22q11.2DS has been reported most related to PD,
other genetic neurodevelopmental disorders have been associated with
neurodegenerative parkinsonism as well, and several shared underlying
mechanisms related to the neurodevelopmental disorder and PD have
been proposed.31 Research of the influence of genetic variants on PD risk
and disease trajectory are crucial for the identification of novel treatment
strategies that may prevent or slow down disease progression. Since
22q11.2DS and other genetic neurodevelopmental disorders are often
identified at an early age, long-term follow up of asymptomatic/pre-
symptomatic individuals may generate knowledge of contributors to the
development of PD and the ability of (environmental) factors to delay or
slow down PD. Studies may include evaluation of parkinsonian symptoms
using the Unified Parkinson’s Disease Rating Scale, prodromal features
such as RMD using polysomnography, and questionnaires for the study
of environmental factors such as diet and exercise. Results may help to
improve counseling of individuals at risk of developing PD. Furthermore,
identification of genetic variants such as 22q11.2DS, that are associated
with an increased risk of PD, facilitates the use of cell and animal models,
32, 33 that may help to identify disease-modifying agents for adults with
22q11.2DS and PD which may also be of relevance to the general population.
Strengths and limitations
Strengths include the large study sample of adults with a, relatively rare,
diagnosis of 22q11.2DS and recruitment from different sites, covering
different regions and organizations. An important limitation includes the
retrospective study design. Under-recognition of PD prevalence may be
related to clinical notes that may have lacked relevant information regarding
a PD diagnosis and the fact that most adults were not screened for PD.
In addition, adults may have had difficulties with signalizing symptoms of
PD and/or seeking help.5 Since genetic testing in adults with an intellectual
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