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大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的。它们可能会影响行为、学习和 运动技能，并与癫痫发作的风险增加有关。的发病率。 神经发育障碍在工业化国家很常见，大约每6名儿童中就有1名受到 导致的情况包括脑瘫、癫痫、注意力缺陷多动障碍、自闭症谱系 精神障碍、智力障碍和学习障碍。研究表明，某些疾病的流行率 神经发育障碍在过去的40年里一直在增加，这对两者都造成了巨大的损失。 个人和社会。尽管更早的识别和干预会改善患者的预后 患有神经发育障碍的儿童，其中许多情况只有在行为方面才能被诊断出来 症状出现，从而限制了研究早期发育和早期干预的机会。至 为了克服这一障碍，我们建议对患有穹隆发育不全(Agcc)的婴儿进行研究。 在6个月前确诊。 这个应用程序的主要目标是描述在 AGCC儿童的前3年生活，利用这一信息确定与 发育迟缓、自闭症谱系障碍(ASD)和/或家庭痛苦的风险增加。2000年有1个 儿童在12个月大时被诊断出患有AGCC，其中许多儿童是在 子宫。AGCC仅由神经解剖学定义，但约30%的AGCC患者将发展为社交 认知缺陷与自闭症一致。由于AGCC可以在出生前被诊断出来，它呈现出一种独特的 有机会了解在自闭症及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带来的风险或保护增加的见解 可以为损害的病因模型提供信息，并潜在地改善预后预测和治疗 包括自闭症在内的社会认知缺陷风险儿童的选择。除了他们的潜在贡献之外 对于自闭症和其他形式的社会障碍的研究和治疗，本申请中的研究提供了 对迄今研究不足的人群、AGCC儿童和他们的 家人。 目前，还没有发表的研究描述一大批患有糖尿病的儿童的早期行为发展。 AGCC，尽管它可以向决定儿童未来的父母提供关键信息 他们未出生的胎儿患有AGCC或决定如何支持患有AGCC的儿童的发育。队列 对成人AGCC的研究揭示了广泛的认知和适应功能。这些变种 看起来基本上是由存在或不存在或其他神经异常引起的，但可能 也受发展因素的影响。然而，在缺乏对早期行为的研究的情况下 在儿童AGCC的发展中，不可能确定与以下方面相关的危险因素或潜在的干预措施 AGCC，给父母留下了心理压力，因为他们的孩子有神经学残疾， 发展轨迹是不可预测的。拟议的研究将为以下方面提供实用信息 临床医生和家长对AGCC表型变异的看法，并建议潜在的干预领域，如 以及关于膝盖骨参与社会认知缺陷的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.