Pathogenetic Insights into Developmental Coordination Disorder Reveal Substantial Overlap with Movement Disorders

Martinica Garofalo; Fleur Vansenne; Deborah A Sival; Dineke S Verbeek

doi:10.3390/brainsci13121625

Pathogenetic Insights into Developmental Coordination Disorder Reveal Substantial Overlap with Movement Disorders

Brain Sci. 2023 Nov 23;13(12):1625. doi: 10.3390/brainsci13121625.

Authors

Martinica Garofalo^{1

2}, Fleur Vansenne^{2

3}, Deborah A Sival^{1

2}, Dineke S Verbeek^{2

3}

Affiliations

¹ Department of Pediatric Neurology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
² Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
³ Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Abstract

Developmental Coordination Disorder (DCD) is a neurodevelopmental condition characterized by non-progressive central motor impairments. Mild movement disorder features have been observed in DCD. Until now, the etiology of DCD has been unclear. Recent studies suggested a genetic substrate in some patients with DCD, but comprehensive knowledge about associated genes and underlying pathogenetic mechanisms is still lacking. In this study, we first identified genes described in the literature in patients with a diagnosis of DCD according to the official diagnostic criteria. Second, we exposed the underlying pathogenetic mechanisms of DCD, by investigating tissue- and temporal gene expression patterns and brain-specific biological mechanisms. Third, we explored putative shared pathogenetic mechanisms between DCD and frequent movement disorders with a known genetic component, including ataxia, chorea, dystonia, and myoclonus. We identified 12 genes associated with DCD in the literature, which are ubiquitously expressed in the central nervous system throughout brain development. These genes are involved in cellular processes, neural signaling, and nervous system development. There was a remarkable overlap (62%) in pathogenetic mechanisms between DCD-associated genes and genes linked with movement disorders. Our findings suggest that some patients might have a genetic etiology of DCD, which could be considered part of a pathogenetic movement disorder spectrum.

Keywords: Developmental Coordination Disorder (DCD); genetics; movement disorders; pathogenetic spectrum.

Grants and funding

University of Groningen and University Medical Center Groningen/M. Garofalo received funding from the Graduate School of Medical Sciences (MD-PhD program) of the University of Groningen and University Medical Center Groningen. The APC was partially funded (10%) by the University of Groningen.