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Review
. 2022 Oct 31;10(1):17-31.
doi: 10.1002/mdc3.13577. eCollection 2023 Jan.

Parkinsonism in Genetic Neurodevelopmental Disorders: A Systematic Review

Emma N M M von Scheibler  1   2 , Agnies M van Eeghen  1   3 , Tom J de Koning  4   5   6 , Mark L Kuijf  7 , Janneke R Zinkstok  8   9   10 , Annelieke R Müller  1   3 , Thérèse A M J van Amelsvoort  2 , Erik Boot  1   2   11
Affiliations
Review

Parkinsonism in Genetic Neurodevelopmental Disorders: A Systematic Review

Emma N M M von Scheibler et al. Mov Disord Clin Pract. .

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 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.

Keywords: Parkinson's disease; genetic; intellectual disability; neurodevelopmental disorder; parkinsonism.

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Conflict of interest statement

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.

Figures

FIG. 1
FIG. 1
Patient characteristics and parkinsonian features in genetic neurodevelopmental disorders that were reported at least 10 times. The complete heat map, including conditions that were reported less than 10 times, is provided in Fig. S2. *The numerator represents how many patients were reported to present with a specific feature, and the denominator represents the number of patients with data available. Additional genetic variants with potential relevance to parkinsonism were reported: a LRRK2, b PRKN, c PRKN. ‐ = unknown.
FIG. 2
FIG. 2
Schematic diagram depicting mechanisms that may underlie parkinsonism in genetic neurodevelopmental disorders, with examples of associated genetic variants.
FIG. 3
FIG. 3
Main messages of the review.
See this image and copyright information in PMC

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References

    1. Hickman RA, O'Shea SA, Mehler MF, Chung WK. Neurogenetic disorders across the lifespan: From aberrant development to degeneration. Nat Rev Neurol 2022;18(2):117–124. 10.1038/s41582-021-00595-5. - DOI - PMC - PubMed
    1. Saudubray JM, Garcia‐Cazorla A. An overview of inborn errors of metabolism affecting the brain: From neurodevelopment to neurodegenerative disorders. Dialogues Clin Neurosci 2018;20(4):301–325. 10.31887/DCNS.2018.20.4/jmsaudubray. - DOI - PMC - PubMed
    1. Morato Torres CA, Wassouf Z, Zafar F, Sastre D, Outeiro TF, Schüle B. The role of alpha‐Synuclein and other Parkinson's genes in neurodevelopmental and neurodegenerative disorders. Int J Mol Sci 2020;21(16):5724. 10.3390/ijms21165724. - DOI - PMC - PubMed
    1. Puschmann A. New genes causing hereditary Parkinson's disease or parkinsonism. Curr Neurol Neurosci Rep 2017;17(9):66. 10.1007/s11910-017-0780-8. - DOI - PMC - PubMed
    1. Morales‐Briceno H, Mohammad SS, Post B, Fois AF, Dale RC, Tchan M, VSC F. Clinical and neuroimaging phenotypes of genetic parkinsonism from infancy to adolescence. Brain 2019;143(3):751‐770. 10.1093/brain/awz345. - DOI - PubMed

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