Early Development in Agenesis of the Corpus Callosum

项目摘要 神经发育障碍是由病理引起的脑功能和结构的异常 在胎儿发育或生命早期影响大脑发育。它们可能会影响行为、学习， 运动技能，并与癫痫发作的风险增加有关。的发生率 在工业化国家，神经发育障碍的发病率很高，大约每6个儿童中就有1个受到神经发育障碍的影响。 由此产生的疾病，包括脑瘫、癫痫、注意力缺陷多动障碍、自闭症谱系 障碍、智力残疾和学习障碍。研究表明，某些疾病的流行 在过去的四十年里，神经发育障碍一直在增加， 个人和社会。虽然早期识别和干预可以改善 患有神经发育障碍的儿童，其中许多情况无法诊断，直到行为 症状出现，从而限制了研究早期发展和早期干预的机会。到 为了克服这一障碍，我们建议研究胼胝体发育不全的婴儿（AgCC） 在6个月大之前被诊断出来。 该应用程序的首要目标是描述在人类发育过程中行为的发展轨迹。 AgCC儿童生命的前3年，使用这些信息来确定与 发育迟缓、自闭症谱系障碍（ASD）和/或家庭窘迫的风险增加。2000年1个 儿童在12个月大时被诊断出患有AgCC，这些儿童中的许多人在 子宫。AgCC仅由神经解剖学定义，但约30%的AgCC患者会发展为社交性 认知缺陷符合自闭症谱系障碍由于AgCC可以在出生前诊断，因此它呈现出独特的 有机会了解在ASD和相关疾病中观察到的社会认知缺陷的早期发展 条件，以及这些发育行为与胼胝体早期组织的关系。 关于AgCC早期神经和行为发育所带来的风险增加或保护的见解 可能为损伤的病因学模型提供信息，并可能改善预后预测和治疗 为有社会认知缺陷风险的儿童提供的选择，包括ASD。除了潜在的贡献外， 研究和治疗ASD和其他形式的社会障碍，本申请中的研究提供 对迄今为止研究不足的人群，患有AgCC的儿童及其 家庭 目前，还没有发表的研究描述了一个大的儿童队列的早期行为发展， AgCC，尽管它可以为决定未来的父母提供关键信息， 他们未出生的胎儿与AgCC或决定如何支持一个孩子与AgCC的发展。队列 对成人AgCC的研究揭示了广泛的认知和适应功能。这些变化 似乎基本上是由存在或不存在或其他神经异常告知，但可能 也受到发展因素的影响。然而，由于缺乏对早期行为的研究， 在患有AgCC的儿童中，不可能确定与以下因素相关的风险因素或潜在干预措施： AgCC，让父母有一个神经残疾的孩子的心理压力， 发展轨迹是不可预测的。这项研究将为以下方面提供实用信息： 临床医生和父母关于AgCC的表型变异，并建议潜在干预的领域， 以及关于胼胝体参与社会认知缺陷发展的新的科学见解。

Project Summary Neurodevelopmental disorders are abnormalities of brain function and structure resulting from pathologies affecting brain development during fetal development or early life. They may affect behaviour, learning, and motor skills, and are associated with an increased risk of epileptic seizures. The incidence of neurodevelopmental disorders is high in industrialised countries, with around 1 in 6 children affected by resulting conditions, including cerebral palsy, epilepsy, attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability and learning disabilities. Research suggests that the prevalence of certain neurodevelopmental disorders has been increasing over the last four decades, with significant costs to both the individual and society. Although earlier identification and intervention leads to improved outcomes for children with neurodevelopmental disorders, many of these conditions cannot be diagnosed until behavioral symptoms appear, thereby limiting opportunities to study early development and early interventions. To overcome this barrier, we are proposing to study infants with agenesis of the corpus callosum (AgCC) diagnosed prior to 6 months of age. The overarching aim of this application is to characterize the developmental trajectory of behavior during the first 3 years of life in children with AgCC, using this information to identify phenotypic factors associated with increased risk of developmental delays, autism spectrum disorder (ASD), and/or familial distress. 1 in 2000 children is diagnosed with AgCC by 12 months of age, and many of these children receive the diagnosis in utero. AgCC is defined only by neuroanatomy, but about 30% of individuals with AgCC will develop social cognitive deficits consistent with ASD. Because AgCC can be diagnosed before birth, it presents a unique opportunity to learn about early development of social cognitive deficits observed in ASD and related conditions, and the relationship of these developing behaviors to early organization of the corpus callosum. Insights regarding increased risk or protection conferred by early neural and behavioral development in AgCC may inform etiological models of impairment and potentially improve prognostic predictions and treatment options for children at risk for social cognitive deficits including ASD. In addition to their potential contributions to research and treatment of ASD and other forms of social impairment, the studies in this application offer significant public health benefit specific to a heretofore understudied population, children with AgCC and their families. Currently, no published research describes early behavioral development in a large cohort of children with AgCC, despite the fact that it could provide critical information to parents who are determining the future of their unborn fetus with AgCC or determining how to support the development of a child with AgCC. Cohort studies of adults with AgCC reveal a broad range of cognitive and adaptive functioning. These variations appear to be substantially informed by the presence or absence or other neurological abnormalities, but may also be influenced by developmental factors. However, in the absence of research on early behavioral development in children with AgCC, it is not possible to identify risk factors or potential interventions relevant to AgCC, leaving parents with the psychological stress of having a neurologically disabled child whose developmental trajectory is unpredictable. The proposed research will provide practical information for clinicians and parents regarding phenotypic variations in AgCC and suggest areas for potential intervention, as well as novel scientific insights regarding callosal involvement in development of social cognitive deficits.