Williams Syndrome: A Neurogenetic Model of Human Behavior


Williams syndrome (WMS) is a rare neurogenetic disorder, usually caused by a deletion at 7q11.23. Integrating the genetic with the distinctive clinical, cognitive, neurophysiological and neuroanatomical profiles of WMS provides an opportunity to understand the molecular basis of human cognition and behavior.

Keywords: Williams syndrome; cognitive phenotype; common deletion; chromosome 7; duplication

Figure 1.

Region of chromosome 7, band 7q11.23, that is commonly deleted in Williams syndrome (WMS) is represented by the solid square. This region is expanded to the right to illustrate its genomic organization, a region of largely single copy genes flanked by a series of genomic duplications.

Figure 2.

Contrasts of drawing and description of an elephant by a teenager with WMS. The dissociation between language and spatial cognition in WMS is evident (full‐scale IQ of 49, verbal IQ of 52 and performance IQ of 54).

Figure 3.

WMS individuals use affective devices in storytelling, compared with subjects with Down syndrome (DNS). Examples from narratives of the Frog, Where Are You? story show the excessive use of narrative evaluative devices in adolescents with WMS.

Figure 4.

Free drawings of houses by age‐ and IQ‐matched adolescents with WMS and DNS show different spatial deficits. The drawings by subjects with WMS contain many parts of houses but the parts are not organized coherently. In contrast, the DNS subjects' drawings are simplified but have the correct overall configuration of houses.

Figure 5.

Block‐design task showing spatial deficits in WMS and DNS. WMS subjects typically show disjointed and fragmented designs, while age‐ and IQ‐matched DNS subjects tend to make errors in internal details while maintaining the overall configuration.

Figure 6.

(a) Line‐ and (b) face‐processing in WMS. The results are shown from two tasks that are both visuoperceptual tasks, where the correct answer requires only pointing to a picture without any constructional component. The contrast in performance on (a) line orientation (Benton judgment of line orientation) and (b) face discrimination (Benton face recognition) is shown for 16 individuals with WMS. On the line‐orientation task, several individuals with WMS could not even pass the warm‐up items. In great contrast, another 16 subjects with WMS perform remarkably well on a very difficult face‐discrimination task that involves recognizing the same individual under different conditions of lighting, shadow and orientation. In both tasks, performance of normal individuals is indicated by the broken lines.

Figure 7.

Neurophysiological markers for language and face processing: (a) ERPs to auditory words and (b) ERPs to upright faces.

Figure 8.

Occipital lobe reduction and preservation of cerebellum. Comparable sagittal MRI brain images from two subjects with WMS and a normal control. The images demonstrate that the occipital lobe, separated from the parietal lobe by the parietal‐occipital sulcus (triangle), is greatly reduced in the subjects with WMS. Relative preservation of cerebellar size in WMS relative to controls is also shown.

Figure 9.

Phenotypic map of WMS. Spaces between vertical lines indicate the regions deleted, and the number of subjects carrying the deletion (i.e. typical deletion, n=146). Square brackets indicate regions that are likely to contain a gene or genes that when deleted contribute in some measure to the characteristic features of WMS. The significance of these data is that deletion of FZD9 through RFC2 does not appear to be associated with the characteristic facial features or cognitive deficits seen in WMS, although it could contribute.


Further Reading

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Bellugi U, Lichtenberger U, Mills D, et al. (1999) Bridging cognition, the brain and molecular genetics: evidence from Williams syndrome. Trends in Neuroscience 22: 197–207.

Botta A, Novelli G, Mari A, et al. (1999) Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD9 genes. Journal of Medical Genetics 36: 478–480.

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Web Links

elastin (supravalvular aortic stenosis, Williams‐Beuren syndrome) (ELN); LocusID: 2006. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2006

elastin (supravalvular aortic stenosis, Williams‐Beuren syndrome) (ELN); MIM number: 130160. OMIM: http://www3.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?130160

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How to Cite close
Korenberg, Julie R, Bellugi, Ursula, Salandanan, Lora S, Mills, Debra L, and Reiss, Allan L(Jul 2006) Williams Syndrome: A Neurogenetic Model of Human Behavior. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005148]