Garofalo Martinica, Vansenne Fleur, Sival Deborah A, Verbeek Dineke S
Department of Pediatric Neurology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
Brain Sci. 2023 Nov 23;13(12):1625. doi: 10.3390/brainsci13121625.
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.
发育性协调障碍(DCD)是一种神经发育障碍,其特征为非进行性中枢运动功能损害。在DCD中已观察到轻度运动障碍特征。到目前为止,DCD的病因尚不清楚。最近的研究表明,一些DCD患者存在遗传基础,但关于相关基因和潜在致病机制的全面知识仍然缺乏。在本研究中,我们首先根据官方诊断标准,在文献中确定了诊断为DCD的患者所描述的基因。其次,我们通过研究组织和时间基因表达模式以及脑特异性生物学机制,揭示了DCD的潜在致病机制。第三,我们探索了DCD与具有已知遗传成分的常见运动障碍(包括共济失调、舞蹈症、肌张力障碍和肌阵挛)之间可能存在的共同致病机制。我们在文献中确定了12个与DCD相关的基因,这些基因在整个脑发育过程中在中枢神经系统中普遍表达。这些基因参与细胞过程、神经信号传导和神经系统发育。DCD相关基因与运动障碍相关基因之间的致病机制存在显著重叠(62%)。我们的研究结果表明,一些患者可能存在DCD的遗传病因,这可被视为致病运动障碍谱系的一部分。