Objective: It is increasingly recognized that individuals with genetic neurodevelopmental disorders (GNDs) such as 22q11.2 deletion syndrome can suffer from parkinsonism. We aim to provide an overview of which of these GNDs are associated with parkinsonism, substantiated with the best available evidence on phenotype, genotype and proposed pathophysiology.

Background: While brain disorders are traditionally dichotomized into neurodevelopmental and neurodegenerative disorders, there is increasing evidence that there is an overlap in its genetic determinants. With advances in clinical genetic testing for neurologic disease, the number of GNDs associated with parkinsonism is growing fast.

Method: We conducted a systematic literature review, and searched PubMed and EMBASE on May 31, 2020. General search terms for GNDs, and a list of genetic mutations associated with a neurodevelopmental disorder as per the Human Phenotype Ontology,[1] were combined with terms for parkinsonism. Study characteristics and descriptive data on GNDs and parkinsonism from the included articles were extracted using a modified version of the Cochrane Consumers and Communication Review Group’s (CCCRG) Data Extraction Template. The review was registered in PROSPERO (registration number CRD42020191035).

Results: Over two hundred full-text publications were selected for data-extraction, reporting on >50 different GNDs and co-morbid parkinsonism. The five most reported GNDs from most to least frequent were: beta-propeller protein-associated neurodegeneration, 22q11.2 deletion syndrome, Down syndrome, cerebrotendinous xanthomatosis, and Rett syndrome.

Conclusion: Many GNDs have been associated with parkinsonism. Therefore, a history of a neurodevelopmental disorder could prompt clinicians to consider genetic testing. Similarly, clinicians who take care of patients with GNDs included in this study should be aware of a possible increased risk of parkinsonism. Further recognition of parkinsonism in these GNDs could provide insights into the mechanisms causing parkinsonism in the general population, crucial for the development of disease-modifying treatments.

References: 1. HumanPhenotypeOntology. Neurodevelopmental abnormality 2019 [Available from: https://hpo.jax.org/app/browse/term/HP:0012759]

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsonism-in-individuals-with-genetic-neurodevelopmental-disorders-a-systematic-review/