Page 18 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 1
in amplitude or speed) with either rigidity (resistance to passive movement,
also called “muscle stiffness”), rest tremor in a limb, or both.44 These motor
symptoms are caused by loss of dopaminergic neurons in the substantia
nigra pars compacta, resulting in dopamine depletion in the striatum.42
Therefore, treatment of Parkinson’s disease includes substitution of
dopamine by a dopamine precursor, such as levodopa. The pathophysiology
of Parkinson’s disease is not completely understood, but seems to result
from an interplay of different factors including aberrant a-synuclein (protein)
aggregation, mitochondrial dysfunction, lysosomal-autophagic dysfunction
and disturbed endosomal trafficking.42, 43 Genetic, epigenetic as well as
environmental factors may contribute to the vulnerability of dopaminergic
neurons to develop Parkinson’s disease.43 Several monogenetic variants
have been associated with Parkinson’s disease, such as SNCA,
45 as well as
the 22q11.2 deletion.46
In addition to Parkinson’s disease, causes of parkinsonism include vascular
pathology, trauma, and medication that negatively affects dopaminergic
neurotransmission (in particular anti-psychotics). It is important to
differentiate these forms of parkinsonism from neurodegenerative
parkinsonism for patient follow-up and treatment. This differentiation may
be challenging in individuals with a GND, because of higher prevalence
rates of co-morbidities, including additional movement or neuropsychiatric
disorders, and polypharmacy.37, 47, 48
A previous study in a large population-based sample of adults with an
intellectual disability indicated a prevalence of Parkinson’s disease and
parkinsonism of 0.4%, two times higher compared to their control group
without intellectual disabilities.49 For adults with 22q11.2DS, there has
been one mono-center study that indicated a 20-70 fold increased risk
of Parkinson’s disease compared to the general population, although in
relatively small sample of adults.46
The sensory system
The sensory system includes visual, auditory, gustatory, olfactory, tactile,
vestibular, proprioceptive and interoceptive systems. Stimuli such as light
or noise are transformed into patterns of neural activity that are centrally
16