Numerical Deficits Across Multiple Genetic Disorders

描述（由申请人提供）：拟议研究的中心目的是调查是否存在与三种神经遗传疾病相关的数值认知缺陷的共同基础：Turner， Williams和全突变脆性X综合征。尽管存在许多差异，但在Turner、Williams、全突变脆性X和22q11.2缺失（心面/DiGeorge）综合征等患者中，一直有数字缺陷的报道。研究人员假设，在这些综合征中，视觉空间功能的一些关键方面受到了干扰，这些基本过程的特征将产生对这些数字缺陷的解释，并可能指出治疗方法。另一方面，这些遗传综合征之间的差异将使研究人员能够控制一系列关键因素，如智力水平、脑容量、心脏状态和其他认知表现领域。

DESCRIPTION (provided by applicant): The central aim of the proposed research is to investigate whether there is a common basis for the numerical cognition deficits associated with three neurogenetic disorders: Turner, Williams, and full mutation fragile X syndromes. Despite many differences, numerical deficits have been consistently reported in individuals with Turner, Williams, full mutation fragile X, and 22q11.2 deletion (velocardiofacial/DiGeorge) syndromes, among others. The investigators hypothesize that some key aspects of visuospatial function are disturbed in each of these syndromes, and characterization of these basic processes will generate explanations of, and possibly indicate treatments for, these numerical deficits. On the other hand, the differences among these genetic syndromes will allow the investigators to control for a range of critical factors such as intelligence level, brain volume, cardiac status, and other cognitive performance domains. This project aims to study seven to fourteen year old children with Williams, Turner, and full mutation fragile X syndromes in parallel with a study of 22q11.2 deletion syndrome children already being carried out by the principal investigator. This will constitute the first parallel study of children with all of these disorders using the same methodology. Thus it has the potential to reveal critical information about a putative "common pathway" for foundational numerical cognitive competence. Little is known about why a set of neurogenetic disorders that produce such different physical and intellectual outcomes should share what appears to be a common deficit in the numerical cognition domain. The investigators' hypothesis is that the disorders all create some form of anomalous in brain development that affects the parietal lobes, as well as other brain areas, in such a way as to disturb the normal development of visual/spatial cognition. Therefore, the investigators propose a program of research in three genetic disorders: Turner, Williams, full mutation fragile X syndromes with the following aims: (1) Characterize the cognitive deficit with performance tests; (2) Specify the volumetric changes in brains of children with these disorders; (3) Determine, via diffusion tensor imaging, white matter anomalies that might contribute to cognitive dysfunction; and (4) Directly measure, via functional magnetic resonance imaging (fMRI), cortical activity as children attempt visuospatial and numerical cognition tasks. The investigators expect that the results of these studies will provide the first extensive explanation of the similarities and/or differences in foundational numerical cognitive processes that exist among these different disorders. Findings are likely to indicate critical neurocognitive factors in the development of normal and disturbed early numerical ability. It should be possible to use these results to develop interventions for children with numerical disabilities and improved teaching methods in the numerical domain for typically developing children.