Page 233 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Summary
Summary
The overall aim of this thesis was to characterize genetic neurodevelopmental
disorders (GNDs) at adult age, with a focus on 22q11.2 deletion syndrome
(22q11.2DS). Study topics included parkinsonism, otolaryngology,
ophthalmology and trauma-related disorders. In this appendix, a summary
of the individual studies is presented. Chapter 1 provides a general
introduction to 22q11.2DS and study topics included in this thesis.
In chapter 2 results are discussed of a systematic review of the literature
on parkinsonism in GNDs. It is increasingly recognized that individuals
with GNDs can suffer from parkinsonism, including neurodegenerative
parkinsonism. With advances in clinical genetic testing for neurologic
disease, the number of GNDs associated with parkinsonism is growing
fast. In this chapter an overview of the literature is provided that reports
on parkinsonism in GNDs. The literature search yielded over two hundred
full-text publications for data-extraction, reporting on 422 individuals
with 69 different GNDs and parkinsonism. The five most reported GNDs
from most to least frequent were: beta-propeller protein-associated
neurodegeneration, 22q11.2DS, Down syndrome, cerebrotendinous
xanthomatosis, and Rett syndrome. Notable findings were an almost equal
male to female ratio, an early median age of motor onset (26 years old),
and rigidity being more common than rest tremor. Results of dopaminergic
imaging and response to antiparkinsonian medication often supported
the neurodegenerative nature of parkinsonism. Moreover, neuropathology
results showed neuronal loss in the majority of cases. Proposed disease
mechanisms included aberrant mitochondrial function and disruptions in
neurotransmitter metabolism, endosomal trafficking, and the autophagic-
lysosomal and ubiquitin-proteasome system. Together, many GNDs have
been associated with parkinsonism and results were often supportive of
neurodegenerative parkinsonism, with typical findings with dopaminergic
imaging and a good response to antiparkinsonian medication. Clinicians
who take care of individuals with GNDs included in this study should be
aware of a possible increased risk of parkinsonism, that may have an
atypical presentation. Similarly, parkinsonism combined with a history
of a neurodevelopmental disorder could prompt clinicians to consider
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