Parkinsonism in Genetic Neurodevelopmental Disorders : A Systematic Review
(2023) In Movement Disorders Clinical Practice 10(1). p.17-31- Abstract
Background: With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms. Methods: A systematic literature review was conducted in PubMed and Embase on June 15, 2021. Search terms for parkinsonism and genetic neurodevelopmental disorders, using generic terms and the Human Phenotype Ontology, were combined. Study characteristics and descriptive data were extracted from the articles using a modified version of the Cochrane... (More)
Background: With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms. Methods: A systematic literature review was conducted in PubMed and Embase on June 15, 2021. Search terms for parkinsonism and genetic neurodevelopmental disorders, using generic terms and the Human Phenotype Ontology, were combined. Study characteristics and descriptive data were extracted from the articles using a modified version of the Cochrane Consumers and Communication Review Group's data extraction template. The protocol was registered in PROSPERO (CRD42020191035). Results: The literature search yielded 208 reports for data-extraction, describing 69 genetic disorders in 422 patients. The five most reported from most to least frequent were: 22q11.2 deletion syndrome, beta-propeller protein-associated neurodegeneration, 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. Conclusion: Parkinsonism has been reported in many GNDs. Findings from this study may provide clues for further research and improve management of patients with GNDs and/or parkinsonism.
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- author
- von Scheibler, Emma N.M.M. ; van Eeghen, Agnies M. ; de Koning, Tom J. LU ; Kuijf, Mark L. ; Zinkstok, Janneke R. ; Müller, Annelieke R. ; van Amelsvoort, Thérèse A.M.J. and Boot, Erik
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- genetic, intellectual disability, neurodevelopmental disorder, Parkinson's disease, parkinsonism
- in
- Movement Disorders Clinical Practice
- volume
- 10
- issue
- 1
- pages
- 17 - 31
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:36699000
- scopus:85141342126
- ISSN
- 2330-1619
- DOI
- 10.1002/mdc3.13577
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: This work was supported financially by Stichting Wetenschappelijk Onderzoek's Heeren Loo (2210100). The funder had no role in the design and conduct of the study, preparation of the review, or approval of the manuscript. The authors report no competing interests. Funding Information: E.B. has received compensation for clinical consultations for the Centre for Consultation and Expertise (CCE) and has received a research grant from the Dutch National Institutes of Health (ZonMw). T.J.d.K. is medical advisor for three non‐profit charities: Stofwisselingskracht foundation (Stichting Stofwisselingskracht), North Sea myoclonus foundation (Stichting Noordzeeziekte) and Janivo Foundation (Janivo Stichting). T.J.d.K. is also medical advisor of Ancora Health BV (profit), a Dutch company delivering lifestyle advice, of which he also holds shares. A.M.v.E is medical advisor of Jazz pharmaceuticals and received funding for "PCOM4RARE; Personalized Outcome Measures for patients with Intellectual Disability" from's Heeren Loo Care Group. J.R.Z. received a research grant from ZonMw and T.A.M.J.v.A. received a research grant from the National Institutes of Health. The other authors have no disclosures to report. Publisher Copyright: © 2022 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- id
- f154101c-e02a-4fbf-8eb7-b11918d08258
- date added to LUP
- 2022-12-12 08:23:35
- date last changed
- 2024-04-18 16:12:05
@article{f154101c-e02a-4fbf-8eb7-b11918d08258,
abstract = {{<p>Background: With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms. Methods: A systematic literature review was conducted in PubMed and Embase on June 15, 2021. Search terms for parkinsonism and genetic neurodevelopmental disorders, using generic terms and the Human Phenotype Ontology, were combined. Study characteristics and descriptive data were extracted from the articles using a modified version of the Cochrane Consumers and Communication Review Group's data extraction template. The protocol was registered in PROSPERO (CRD42020191035). Results: The literature search yielded 208 reports for data-extraction, describing 69 genetic disorders in 422 patients. The five most reported from most to least frequent were: 22q11.2 deletion syndrome, beta-propeller protein-associated neurodegeneration, 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. Conclusion: Parkinsonism has been reported in many GNDs. Findings from this study may provide clues for further research and improve management of patients with GNDs and/or parkinsonism.</p>}},
author = {{von Scheibler, Emma N.M.M. and van Eeghen, Agnies M. and de Koning, Tom J. and Kuijf, Mark L. and Zinkstok, Janneke R. and Müller, Annelieke R. and van Amelsvoort, Thérèse A.M.J. and Boot, Erik}},
issn = {{2330-1619}},
keywords = {{genetic; intellectual disability; neurodevelopmental disorder; Parkinson's disease; parkinsonism}},
language = {{eng}},
number = {{1}},
pages = {{17--31}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Movement Disorders Clinical Practice}},
title = {{Parkinsonism in Genetic Neurodevelopmental Disorders : A Systematic Review}},
url = {{http://dx.doi.org/10.1002/mdc3.13577}},
doi = {{10.1002/mdc3.13577}},
volume = {{10}},
year = {{2023}},
}