Developmental Coordination Disorder (DCD) means the presence of motor problems interfering with daily activities in the absence of evident neurological pathology.¹ It affects 5–6% of children and it is often accompanied by other neurodevelopmental disorders, such as attention deficit hyperactivity disorder or autism spectrum disorder.¹ It often has been suggested that DCD runs in families, but only recently some evidence of a possible genetic background of DCD has been presented.² The Dutch Lifelines Cohort study³ offered the opportunity to address the question of whether the risk of DCD runs in families.

Lifelines is a multi-disciplinary prospective population-based cohort study examining in a unique three-generation design the health and health-related behaviours of 167 729 persons living in the North of the Netherlands. It employs a broad range of investigative procedures in assessing the biomedical, socio-demographic, behavioural, physical and psychological factors which contribute to the health and disease of the general population, with a special focus on multi-morbidity and complex genetics.³ The Lifelines Cohort study has been approved by the ethical committee of the University Medical Center Groningen, the Netherlands (METC 2007/152).

In 2017 all parents participating in Lifelines, with children aged 5–12 years (n = 5479) received the Dutch translation of the DCD Questionnaire 2007.⁴ This is a widely used instrument to screen for DCD with 15 questions addressing control during movement, fine motor activities, including handwriting, and general coordination. We used available age-based percentiles to classify children as at risk of DCD (rDCD).⁴ Children with diagnoses not compatible with DCD, for example, cerebral palsy, were excluded from the analysis, resulting in a total of adequately completed questionnaires on 1722 children (31.4%), coming from 1255 different families (each having 1–4 children in the sample; see Table 1 and Appendix S1). From the 1722 children, 223 were classified as rDCD. The proportion of rDCD in children with no siblings in the data set was 13.38% (see Appendix S1).

We calculated the probability of observing the number of children classified as rDCD and non-rDCD in each of the 418 families with two or more children present in our data under the assumption of rDCD not running in the family. That is, we tested whether the probability of a child having rDCD was independent of having a sibling with rDCD. For mathematical details on the statistical approach and the use of one-sample Chi-square tests to arrive at an overall p-value for this probability, we refer to Appendix S1. Our analysis resulted in an overall probability of rDCD occurring independently in our data of p = 0.008. This is a very small p-value, implying that our data do not support the assumed hypothesis of rDCD occurring independently within families. As our data show a tendency towards observing more rDCD children within families than expected, we conclude that our data suggest being at risk of DCD runs in families.

This means that our data support evidence of the existence of familial predisposition to DCD, which might include genetic variants playing a pathogenetic role.² In other words, genetic susceptibility for motor impairment may be one of the steps in the multifactorial pathway of DCD. Well-known risk factors in the aetiological pathway are male gender and pre-term birth.⁵ Conceivably, the multifactorial pathway varies among children with DCD, a diagnosis that by itself is an umbrella term covering children with various types of motor problems, for example, fine motor impairments or balance problems.¹

The strength of our study is its two-generation design and the use of a large population-based cohort. However, the study also has limitations. First, our response rate was 31.4%, which reduces the generalizability of the findings. We cannot rule out the potential effect of selection bias either, although the direction of its effect on our conclusion is not clear. In general, parents may be more inclined to respond when already suspecting their offspring to be at risk for DCD. This would increase the observed proportion of children with rDCD overall in the data. However, this effect would simultaneously imply that the benchmark of 13.38% against which we tested our hypothesis of independence would be positively biased as well, which in turn would make it harder to reach a significant result in our test. Lastly, we did not diagnose DCD but only were able to evaluate whether children were at risk of DCD.

In conclusion, our findings support emerging evidence that the risk of DCD may run in families.

发育协调障碍 (DCD) 是指在没有明显的神经病理学情况下，存在干扰日常活动的运动问题。¹它影响 5-6% 的儿童，并且通常伴有其他神经发育障碍，例如注意力缺陷多动障碍或自闭症谱系障碍。¹人们经常认为 DCD 具有家族遗传性，但直到最近才出现了一些表明 DCD 可能存在遗传背景的证据。²荷兰生命线队列研究³提供了解决 DCD 风险是否在家庭中遗传这一问题的机会。

Lifelines 是一项基于人群的多学科前瞻性队列研究，以独特的三代设计检查居住在荷兰北部的 167,729 人的健康和健康相关行为。它采用广泛的调查程序来评估生物医学、社会人口、行为、身体和心理因素，这些因素有助于一般人群的健康和疾病，特别关注多种发病率和复杂的遗传学。³生命线队列研究已获得荷兰格罗宁根大学医学中心伦理委员会的批准 (METC 2007/152)。

2017 年，所有参与生命线的 5-12 岁儿童家长 ( n  = 5479) 都收到了 2007 年 DCD 问卷的荷兰语翻译^。4这是一种广泛使用的 DCD 筛查工具，有 15 个问题，涉及运动过程中的控制、精细等问题。运动活动，包括书写和一般协调。我们使用现有的基于年龄的百分位数将儿童分类为有患 DCD (rDCD) 风险的儿童。⁴诊断不符合 DCD 的儿童（例如脑瘫）被排除在分析之外，从而对来自 1255 个不同家庭（每个家庭有 1-4 名儿童）的 1722 名儿童（31.4%）进行了充分填写的问卷调查。样品；见表1和附录S1）。在 1722 名儿童中，有 223 名被归类为 rDCD。数据集中无兄弟姐妹的儿童rDCD比例为13.38%（见附录S1）。

我们计算了数据中 418 个有两个或更多孩子的家庭中每个家庭中被分类为 rDCD 和非 rDCD 的孩子数量的概率，假设家庭中没有 rDCD。也就是说，我们测试了孩子患有 rDCD 的概率是否与兄弟姐妹患有 rDCD 无关。有关统计方法的数学细节以及使用单样本卡方检验得出该概率的总体 p 值的信息，请参阅附录 S1。我们的分析得出 rDCD 在我们的数据中独立发生的总体概率为p  = 0.008。这是一个非常小的 p 值，意味着我们的数据不支持 rDCD 在家庭内独立发生的假设。由于我们的数据显示，家庭中观察到的 rDCD 儿童数量多于预期，因此我们的结论是，我们的数据表明家庭中存在 DCD 患病风险。

这意味着我们的数据支持存在 DCD 家族易感性的证据，其中可能包括发挥致病作用的遗传变异。²换句话说，运动障碍的遗传易感性可能是 DCD 多因素途径中的步骤之一。病因学途径中众所周知的危险因素是男性和早产。⁵可以想象，患有 DCD 的儿童的多因素途径各不相同，这种诊断本身就是一个涵盖性术语，涵盖患有各种类型运动问题的儿童，例如精细运动障碍或平衡问题。¹

我们研究的优势在于其两代设计和大量基于人群的队列的使用。然而，这项研究也有局限性。首先，我们的回复率为 31.4%，这降低了研究结果的普遍性。我们也不能排除选择偏差的潜在影响，尽管它对我们结论的影响方向尚不清楚。一般来说，当父母已经怀疑自己的后代有患发展性协调障碍的风险时，他们可能更倾向于做出反应。这将增加数据中观察到的 rDCD 儿童的总体比例。然而，这种效应同时意味着我们测试独立性假设所依据的 13.38% 基准也将出现正偏差，这反过来又会使我们的测试更难获得显着结果。最后，我们没有诊断 DCD，只是能够评估儿童是否有患 DCD 的风险。

总之，我们的研究结果支持了新出现的证据表明 DCD 风险可能在家庭中遗传。