Summary of work: Specific genetic or hormonal abnormalities during human development produce mental retardation syndromes with specific cognitive patterns, allowing one to map genetic expression onto brain development. Correlational and discriminant functions of brain glucose metabolism measured with positron emission tomography (PET) showed disrupted brain language areas in young adults with Down's syndrome (DS). DS subjects activated similar brain areas during language processing as controls, but to a lesser extent. Subjects with full Turner syndrome (TS) (45,X) had reduced volumes of the hippocampus and of left cerebral hemisphere, measured with magnetic resonance imaging (MRI), and impaired memory and visuospatial abilities. Mosaic Turner subjects had brain volume reductions between full Turner syndrome subjects and controls, indicating gene dosage effects on brain development. Individuals with a premutation for fragile X syndrome [fra(X)] had abnormal patterns of brain glucose metabolism that correspond to behavioral and cognitive changes.