Objective: To explore the underlying pathogenetic mechanisms of Developmental Coordination Disorder (DCD) and compare these with findings in ataxia, dystonia and myoclonus.

Background: DCD is a neurodevelopmental condition characterized by non-progressive incoordination. According to the criterion D of the DSM-5,[1] DCD cannot be attributed to neurological conditions affecting movement. However, mild ataxic, dystonic and/or myoclonic features are occasionally observed. [2] Despite recent studies suggesting the possibility of a genetic substrate for DCD,[3] the pathogenesis of DCD still remains unclear. In this study, we explored the pathogenetic mechanisms of DCD, with the hypothesis that they may overlap with those of co-occurring movement disorders, such as ataxia, dystonia and myoclonus.

Method: After identifying genes and loci associated with DCD in literature, we performed brain-specific gene co-expression, biological pathway enrichment, temporal and tissue-specific gene expression analyses. Afterwards, we compared these results with our previous findings in ataxia, dystonia and myoclonus.

Results: In literature, twelve genes and eight loci were associated with DCD. Ten genes from the brain-specific co-expression network were known ataxia, dystonia and myoclonus genes. Most of the significantly enriched biological pathways in DCD were related to nervous system development, neural signaling and cellular organization processes. The 20 most significant biological processes in DCD showed a 55%, 40%, 60% and 65% overlap with those in ataxia, dystonia, ataxia-dystonia and myoclonus, respectively. DCD-associated genes were highly expressed in the central nervous system during brain development.

Conclusion: Our findings show a remarkable overlap in biological pathways and gene expression patterns between DCD, ataxia, dystonia and myoclonus. This suggests that the pathogenetic substrate of DCD could belong to a movement disorder spectrum, in contradiction with the DSM-5 definition of DCD.

References: 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013;5(5).
2. Lawerman TF, Brandsma R, Maurits NM, et al. Paediatric motor phenotypes in early-onset ataxia, developmental coordination disorder, and central hypotonia. Developmental Medicine & Child Neurology. 2020;62(1):75-82.
3. Mosca SJ, Langevin LM, Dewey D, et al. Copy-number variations are enriched for neurodevelopmental genes in children with developmental coordination disorder. Journal of Medical Genetics. 2016;53(12):812-9.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/overlapping-pathogenetic-findings-in-developmental-coordination-disorder-dcd-ataxia-dystonia-and-myoclonus-is-dcd-part-of-a-movement-disorder-spectrum/