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Williams Syndrome: A Genetic Deletion Disorder Presenting Clues to the Biology of Sociability and Clinical Challenges of Hypersociability

  • Stephen I. Deutsch, Richard B. Rosse and Barbara L. Schwartz


Williams syndrome is a neurodevelopmental disorder that results from the deletion of ~25-30 genes spanning about 1.5 megabases in the q11.23 region of chromosome 7. Patients with this syndrome present with a combination of a distinctive elfin-like facial appearance; growth retardation; mild mental retardation; an inconsistent cognitive profile that includes visuospatial impairments with good facial discrimination and relatively preserved expressive language skills; and cardiovascular abnormalities. In addition, a striking behavioral feature of the syndrome is the high sociability and empathy that these patients show for others. The study of patients with “partial” deletions of the chromosome band 7q11.23, mutated genes in this region and knockout mice with deletions of specific genes in the homologous G1–G2 region of mouse chromosome 5 are clarifying some genotype/phenotype relationships. Futhermore, genes located in this region that are prominently expressed have been implicated in brain development and function.The neuropsychological profile of patients with Williams syndrome is heterogeneous, highlights important dissociations between cognitive functions and suggests that the behavioral dimensions of sociability, empathy, engageability, and talkativeness may be independent of, or not easily explained by, the cognitive deficits. Williams syndrome has enormous heuristic value because its pathological feature of heightened “sociability” can be a “deficit” symptom of major complex neuropsychiatrie disorders, such as schizophrenia and autism. Data consistent with a core inability of patients with Williams syndrome to inhibit social approach suggest that this disorder may afford an opportunity to study the biological basis of the “drive” toward socialization. From a research perspective, the syndrome lends itself to neurobiological studies of sociability as a dimension that varies independently of cognition (or at least many separable cognitive processes). Importantly, from a clinical perspective, the syndrome challenges us to administer strategic psychosocial interventions that take advantage of the opportunities that “pathological” sociability provide, while avoiding its threats. An illustrative example of an effective strategically planned psychosocial intervention for a patient with Williams syndrome is briefly presented.


Corresponding author

Please direct all correspondence to: Stephen I. Deutsch, MD, PhD, Department of Veterans Affairs Medical Center, Mental Health Service Line, 50 Irving Street, NW, Washington, DC 20422; Tel: 202-745-8156, Fax: 202-745-8169; E-mail:


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1.Tassabehji, M. Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet. 2003;12:R229R237.
2.Reiss, AL, Eckert, MA, Rose, FE, et al.An experiment of nature: brain anatomy parallels cognition and behavior in Williams syndrome. J Neurosci. 2004;24:50095015.
3.Meyer-Lindberg, A, Mervis, CB, Berman, KF. Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behavior. Nat Rev Neurosci. 2006;7:380393.
4.Mervis, C, Klein-Tasman, BP. Williams Syndrome: cognition, personality, and adaptive behavior. Ment Retard Dev Disabil Res Rev. 2000;6:148158.
5.Mervis, CB, Becerra, AM. Language and communicative development in Williams syndrome. Ment Retard Dev Disabil Res Rev. 2007;13:315.
6.Bellugi, U, Bihrle, A, Jernigan, T, Trauner, D, Doherty, S. Neuropsychological, neurological, and neuroanatomical profile of Williams syndrome. Am J Med Genet Suppl. 1990;6:115125.
7.Deruelle, C, Mancini, J, Livet, MO, Casse-Perrot, C, de Schonen, S. Configural and local processing of faces in children with Williams syndrome. Brain Cogn. 1999;41:276298.
8.Porter, MA, Coltheart, M. Global and local processing in Williams syndrome, autism, and Down syndrome: perception, attention, and construction. Dev Neuropsychol. 2006;30:771789.
9.Frigerio, E, Burt, DM, Gagliardi, C, et al.Is everybody always my friend? Perception of approachability in Williams syndrome. Neuropsychologia. 2006;44:254259.
10.Hopyan, T, Dennis, M, Weksberg, R, Cytrynbaum, C. Music skills and the expressive interpretation of music in children with Williams-Beuren syndrome: Pitch, rhythm, melodic imagery, phrasing and musical affect. Child Neuropsychol. 2001;7:4253.
11.Pearlman-Avnion, S, Eviatar, Z. Narrative analysis in developmental social and linguistic pathologies: dissociation between emotional and informational language use. Brain Cogn. 2002;48:494499.
12.Porter, MA, Coltheart, M, Langdon, R. The neuropsychological basis of hypersociability in Williams and Down syndrome. Neuropsychologia. 2007;45:28392849.
13.Mobbs, D, Eckert, MA, Mills, D, et al.Frontostriatal dysfunction during response inhibition in Williams syndrome. Biol Psychiatry. 2007;62:256261.
14.Hinsley, TA, Cunliffe, P, Tipney, HJ, Brass, A, Tassabehji, M. Comparison of TFII-I gene family members deleted in Williams-Beuren syndrome. Protein Sci. 2004;13:25882599.
15.Makeyev, AV, Erdenechimeg, L, Mungunsukh, O, et al.GTF2IRD2 is located in the Williams-Beuren syndrome critical region 7q11.23 and encodes a protein with two TFII-I-like helix-loop-helix repeats. Proc Natl Acad Sci USA. 2004;101:1105211057.
16.Tassabehji, M, Hammond, P, Karmiloff-Smith, A, et al.GTF2IRD1 in craniofacial development of humans and mice. Science. 2005;310:11841187.
17.van Hagen, JM, van der Geest, JN, van der Giessen, RS, et al.Contribution of CYLN2 and GTF2IRD1 to neurological and cognitive symptoms in Williams syndrome. Neurobiol Dis. 2007;26:112124.
18.Palmer, SJ, Tay, ESE, Santucci, N, et al.Expression of Gtf2ird1, the Williams syndrome-associated gene, during mouse development. Gene Expr Patterns. 2007;7:396404.
19.Meyer-Lindenberg, A, Kohn, P, Mervis, CB, et al.Neural basis of genetically determined visuospatial construction deficit in Williams syndrome. Neuron. 2004;43:623631.
20.Gagliardi, C, Frigerio, E, Burt, DM, Cazzaniga, I, Perrett, DI, Borgatti, R. Facial expression recognition in Williams syndrome. Neuropsychologia. 2003;41:733738.
21.Davies, M, Howlin, P. Adults with Williams syndrome: preliminary study of social, emotional and behavioural difficulties. Br J Psychiatry. 1998;172:273276.

Williams Syndrome: A Genetic Deletion Disorder Presenting Clues to the Biology of Sociability and Clinical Challenges of Hypersociability

  • Stephen I. Deutsch, Richard B. Rosse and Barbara L. Schwartz


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