Brain Structure/Function in Children with Oral Clefts

口裂儿童的大脑结构/功能

• 批准号: 6655044
• 负责人: PEGGY C NOPOULOS
• 金额: $ 35.03万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655044
• 关键词: adolescence (12-20); behavior test; brain morphology; cerebellum; cerebrum; child (0-11); cleft lip; cleft palate; clinical research; cognition disorders; gene expression; genetic screening; genotype; interview; magnetic resonance imaging; patient oriented research; phenotype

DESCRIPTION (provided by applicant): This study is designed to evaluate brain structure and function in children with non-syndromic clefts of the lip and/or palate (NSCLP). In addition, the study will evaluate the relationship between measures of brain structure/function and genes associated with oral clefts. The etiology of non-syndromic oral clefts is complex, involving both genetic and environmental factors. Cognitive dysfunction is frequently associated with oral clefts. In syndromic clefting disorders, cognitive dysfunction is ubiquitous and often severe (mental retardation). The cognitive dysfunction associated with non-syndromic clefts is less severe but should not be underestimated. The fact that clefts of the lip and/or palate are associated with structural brain abnormalities is intuitive as the development of the brain and face are intimately related. However, the systematic study of the types of brain anomalies present in patients with clefts of the lip and/or palate (and the functional consequences thereof) has been almost completely overlooked. In the first study of its kind, the principal investigator of this grant has evaluated brain structure and function using Magnetic Resonance Imaging (MRI) in a group of adult males with NSCLP. The findings from that study indicate a pattern of cognitive dysfunction involving language and executive functions. In addition, there were robust abnormalities in volume and tissue composition of the cerebrum and cerebellum. Moreover, the abnormalities in brain structure were directly related to the abnormalities in cognitive function. Several studies have documented the cognitive dysfunction of children with NSCLP. Findings include global mild deficits with specific problems with language function. Although it has been hypothesized that these abnormalities are due to a primary problem in brain structure and function, no study to date has evaluated brain structure in this population. Evaluating brain structure in this group and its relationship to brain function will be key information to the search for understanding the neurobiology of cognitive dysfunction in this group. In addition, several genes have been associated with non-syndromic oral clefting and may play a key role in its pathoetiology (e.g. MSX1, TGFB3, TGFA). It is likely that the genetic determinants of non-syndromic clefting are related to the accompanying abnormalities in brain structure and function. Evaluating the relationship between brain structure/function and genes known to be associated with non-syndromic clefts may shed light on possible etiologic mechanisms at the molecular level.

描述（由申请人提供）：本研究旨在评估患有非综合征性唇裂和/或腭裂（NSCLP）的儿童的大脑结构和功能。 此外，该研究还将评估大脑结构/功能测量与口腔裂相关基因之间的关系。 非综合征性唇裂的病因很复杂，涉及遗传和环境因素。认知功能障碍通常与唇裂有关。在综合征性裂隙障碍中，认知功能障碍普遍存在，而且往往很严重（精神发育迟滞）。与非综合征性裂隙相关的认知功能障碍不太严重，但不应低估。唇裂和/或腭裂与大脑结构异常相关这一事实是直观的，因为大脑和面部的发育密切相关。然而，对唇裂和/或腭裂患者大脑异常类型（及其功能后果）的系统研究几乎完全被忽视。 在此类研究中，这项资助的主要研究人员使用磁共振成像 (MRI) 对一组患有 NSCLP 的成年男性进行了大脑结构和功能的评估，这在同类研究中尚属首次。该研究的结果表明了一种涉及语言和执行功能的认知功能障碍模式。此外，大脑和小脑的体积和组织成分也存在严重异常。而且，大脑结构的异常与认知功能的异常有直接关系。 多项研究记录了患有 NSCLP 的儿童的认知功能障碍。研究结果包括全球轻度缺陷以及语言功能的特定问题。尽管有人假设这些异常是由于大脑结构和功能的主要问题造成的，但迄今为止还没有研究评估过该人群的大脑结构。评估该群体的大脑结构及其与大脑功能的关系将是寻求了解该群体认知功能障碍的神经生物学的关键信息。 此外，一些基因与非综合征性口裂相关，可能在其病理学中发挥关键作用（例如 MSX1、TGFB3、TGFA）。非综合征性脑裂的遗传决定因素可能与伴随的大脑结构和功能异常有关。评估大脑结构/功能与已知与非综合征性裂隙相关的基因之间的关系可能会在分子水平上揭示可能的病因机制。