Page 233 - Demo

Summary231A1 SummaryThe 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 autophagiclysosomal 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