Williams syndrome: a relationship between genetics, brain morphology and behaviour


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Abstract

BackgroundGenetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ˜28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual deficiencies (i.e. low-moderate intelligence quotient, visuospatial deficits) yet relatively preserving what is uniquely human (i.e. language and social-emotional cognition). Therefore, WS provides a privileged setting for investigating the relationship between genes, brain and the consequent complex human behaviour.MethodsWe used in vivo anatomical magnetic resonance imaging analysing cortical surface-based morphometry, (i.e. surface area Symbol, cortical volume Symbol, cortical thickness Symbol, gyrification index Symbol) and cortical complexity Symbol, which is of particular relevance to the WS genotype–phenotype relationship in 22 children (2.27–14.6 years) to compare whole hemisphere and lobar surface-based morphometry between WS (n = 10) and gender/age matched normal controls healthy controls (n = 12).ResultsCompared to healthy controls, WS children had a (1) relatively preserved Cth; (2) significantly reduced SA and CV; (3) significantly increased GI mostly in the parietal lobe; and (4) decreased CC specifically in the frontal and parietal lobes.ConclusionOur findings are then discussed with reference to the Rakic radial-unit hypothesis of cortical development, arguing that WS gene deletions may spare Cth yet affecting the number of founder cells/columns/radial units, hence decreasing the SA and CV. In essence, cortical brain structure in WS may be shaped by gene-dosage abnormalities.

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