ABSTRACT
Williams syndrome (WS) is a neurodevelopmental disorder resulting from a hemizygous deletion of chromosome 7q11.23. The phenotype of WS consists of typical dysmorphic features, supravalvular aortic stenosis, infantile hypercalcemia and growth retardation. While language and facial recognition seem to be relatively spared, visuospatial constructive disabilities are a hallmark of the neurobehavioral profile of WS. In order to search for actual structural abnormalities underlying this precisely defined neurodevelopmental disorder, we performed anatomical magnetic resonance imaging (MRI) in 9 WS children (11.6 +/- 3.1 years; age range: 5.5-15 years) and 11 normal age-matched control children (11.8 +/- 2.2 years; age range: 8-15 years) using voxel-based morphometry (VBM). VBM is a fully automated whole-brain technique that delivers a voxel-wise assessment of regional grey and white matter concentration. A significant decrease in grey matter concentration was detected in the left parieto-occipital region of WS children (P < 0.05 corrected height threshold). The location of this abnormality in WS children coincides with the location of the structural abnormality previously described using the same method in 13 WS adults. These parieto-occipital abnormalities are consistent with the cognitive profile of WS which includes severe visuospatial construction and numerical cognition deficits. The demonstration of identical structural abnormalities in both adults and children argues for their early origin. Additionally, our study provides support for the use of advanced structural imaging techniques in children, in order to improve our understanding of neurobehavioral phenotypes associated with well-defined genetic disorders.
