Magnetic resonance spectroscopy was used to study brain biochemistry in 14 patients (age, 8-37 years) with Williams syndrome (WS) compared to 48 controls at the MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, UK. All patients had the facial dysmorphology typical of WS, and all showed the uneven cognitive-linguistic profile in psychological testing, with relative sparing of language and verbal skills and deficits in visuospatial, nonverbal tasks such as number, spatial cognition, planning, and problem solving. All WS subjects showed decreases in the phosphomonoester (PME) peak in 31P MRS ratios. Decreasing PME is associated with decreased cognitive performance. Ratios of choline- and creatine-containing compounds to N-acetylaspartate (Cho/Na and Cre/Na) were significantly elevated in the cerebellum of WS subjects, while the Cho/Cre ratio was not altered. The increased Na-containing ratios and suggested decrease in the cerebellar N-acetylaspartate (NA), a neuronal marker, correlated with impaired tests of cognitive ability, especially speed of processing. Cerebellar neuronal integrity may be important in cognition. [1]

COMMENT. Williams syndrome (WS) is a rare genetic dysmorphic disorder with a hemizygous deletion on chromosome 7 and delayed motor and cognitive development. The chromosome abnormality affects a gene that programs elastin, accounting for the characteristic premature aging and wrinkles on the face, elfin facies, hernias, and supravalvular aortic stenosis. Adjacent genes included in the deletion may account for the mild mental retardation, visuospatial impairments, and disproportionate abilities in music and language [2]. Biochemical abnormalities in the brain, demonstrated by magnetic resonance spectroscopy, show correlations with cognitive testing that may be specific for cerebellar dysfunction or may represent a more global cerebral anomaly. The dissociation between language and cognitive skills presents a specific neuropsychologic profile for WS. In one report, seizures occurred in 50% of cases (See Progress in Pediatric Neurology I, PNB Publ, 1991;p318).