Human models exist in which genetic or hormonal dysfunction results in specific brain changes leading to specific mental retardation syndromes. Correlational analysis and multiple regression and discriminant function analyses of brain glucose utilization data as measured with positron emission tomography (PET) show that brain language areas are disrupted in young adults with Down syndrome. Down syndrome subjects use similar regions to process language as controls, but to a lesser extent. Subjects with Turner syndrome (45,X), including mosaics, had reduced volume of the hippocampus as measured with magnetic resonance imaging, and impairment of memory and visuospatial abilities. Mosaic Turner syndrome subjects had volumes of left cerebral hemisphere and subcortical nuclei, and metabolism of left middle temporal region and right/left metabolic asymmetry ratios in parietal region intermediate between full Turner syndrome subjects and controls. The cognitive profile in fragile X syndrome is distinct from that in other forms of mental retardation. In this syndrome there is an enlarged brain on MRI and altered functional metabolic interactions among frontal and subcortical brain regions; focal changes in brain structure and metabolism may be related to cognitive changes.
