Hostname: page-component-8448b6f56d-jr42d Total loading time: 0 Render date: 2024-04-23T10:52:08.149Z Has data issue: false hasContentIssue false
  • English
  • Français

Defining the social phenotype in Williams syndrome: A model for linking gene, the brain, and behavior

Published online by Cambridge University Press:  23 January 2008

Anna Järvinen-Pasley ,
Ursula Bellugi ,
Judy Reilly ,
Debra L. MILLS ,
Albert Galaburda ,
Allan L. Reiss  and
Julie R. Korenberg
Anna Järvinen-Pasley
Affiliation:
Salk Institute for Biological Studies
Ursula Bellugi*
Affiliation:
Salk Institute for Biological Studies
Judy Reilly
Affiliation:
San Diego State University University of Poitiers, France
Debra L. MILLS
Affiliation:
Emory University
Albert Galaburda
Affiliation:
Beth Israel Deaconess Medical Center
Allan L. Reiss
Affiliation:
Stanford University School of Medicine
Julie R. Korenberg
Affiliation:
Cedars-Sinai Medical Center
*
Address correspondence and reprint requests to: Ursula Bellugi, Laboratory for Cognitive Neuroscience, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099; E-mail: bellugi@salk.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

Research into phenotype–genotype correlations in neurodevelopmental disorders has greatly elucidated the contribution of genetic and neurobiological factors to variations in typical and atypical development. Etiologically relatively homogeneous disorders, such as Williams syndrome (WS), provide unique opportunities for elucidating gene–brain–behavior relationships. WS is a neurogenetic disorder caused by a hemizygous deletion of approximately 25 genes on chromosome 7q11.23. This results in a cascade of physical, cognitive–behavioral, affective, and neurobiological aberrations. WS is associated with a markedly uneven neurocognitive profile, and the mature state cognitive profile of WS is relatively well developed. Although anecdotally, individuals with WS have been frequently described as unusually friendly and sociable, personality remains a considerably less well studied area. This paper investigates genetic influences, cognitive–behavioral characteristics, aberrations in brain structure and function, and environmental and biological variables that influence the social outcomes of individuals with WS. We bring together a series of findings across multiple levels of scientific enquiry to examine the social phenotype in WS, reflecting the journey from gene to the brain to behavior. Understanding the complex multilevel scientific perspective in WS has implications for understanding typical social development by identifying important developmental events and markers, as well as helping to define the boundaries of psychopathology.

Type
Research Article
Information
Development and Psychopathology , Volume 20 , Issue 1 , Winter 2008 , pp. 1 - 35
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This research is based largely on our studies stemming from NIH Program Project PO1 NICHD 33113. Projects include molecular genetics (J.R.K.), neurophysiology (D.M.), functional neuroanatomy (A.L.R.), cellular architectonics (A.G.), and neurocognitive characterization (U.B., in association with A.J.P. and J.R.).

References

Adolphs, R. (2001). The neurobiology of social cognition. Current Opinion in Neurobiology, 11, 231–239.CrossRefGoogle ScholarPubMed
Adolphs, R. (2003). Cognitive neuroscience of human social behavior. Nature Reviews Neuroscience, 4, 165–178.CrossRefGoogle Scholar
Adolphs, R., Tranel, D., & Damasio, A. R. (1998). The human amygdala in social judgment. Nature, 393, 470–474.CrossRefGoogle ScholarPubMed
Baldwin, D. A. (1991). Infants' contribution to the achievement of joint reference. Child Development, 62, 875–890.CrossRefGoogle Scholar
Bauman, M. D., Lavenex, P., Mason, W. A., Capitanio, J. P., & Amaral, D. G. (2004). The development of mother–infant interactions after neonatal amygdala lesions in rhesus monkeys. The Journal of Neuroscience, 24, 711–721.CrossRefGoogle ScholarPubMed
Beery, K. E. (1989). Developmental Test of Visuo–Motor Integration (3rd rev.). Cleveland, OH: Modern Curriculum Press.Google Scholar
Bellugi, U., Adolphs, R., Cassady, C., & Chiles, M. (1999). Towards the neural basis for hypersociability in a genetic syndrome. NeuroReport, 10, 1653–1657.CrossRefGoogle Scholar
Bellugi, U., Lichtenberger, L., Jones, W., Lai, Z., & St. George, M. (2000). The neurocognitive profile of Williams syndrome: A complex pattern of strengths and weaknesses. Journal of Cognitive Neuroscience, 12 (Suppl. 1), 7–29.CrossRefGoogle ScholarPubMed
Bellugi, U., Lichtenberger, L., Mills, D., Galaburda, A., & Korenberg, J. R. (1999). Bridging cognition, the brain and molecular genetics: Evidence from Williams syndrome. Trends in Neurosciences, 22, 197–207.CrossRefGoogle ScholarPubMed
Benton, A. L., Hamsher, K. de S., Varney, N. R., & Spreen, O. (1983). Contributions to neuropsychological assessment. New York: Oxford University Press.Google Scholar
Beuren, A. J., Apitz, J., & Harmjanz, D. (1962). Supravalvular aortic stenosis in association with mental retardation and a certain facial appearance. Circulation, 26, 1235–1240.CrossRefGoogle Scholar
Bishop, D. V. M. (1997). Cognitive neuropsychology and developmental disorders: Uncomfortable bedfellows. Quarterly Journal of Experimental Psychology, 50A, 899–923.CrossRefGoogle Scholar
Boersma, P. (2001). PRAAT, a system for doing phonetics by computer. Glot International, 5, 341–345. Retrieved from http://www.praat.org/Google Scholar
Bongiovanni, A. M., Eberlein, W. R., & Jones, I. T. (1957). Idiopathic hypercalcemia of infancy, with failure to thrive; Report of three cases, with a consideration of the possible etiology. New England Journal of Medicine, 257, 951–958.CrossRefGoogle ScholarPubMed
Botta, A., Novelli, G., Mari, A., Novelli, A., Sabani, M., Korenberg, J., et al. (1999). Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. Journal of Medical Genetics, 36, 478–480.Google Scholar
Brock, J. (2007). Language abilities in Williams syndrome: A critical review. Development and Psychopathology, 19, 97–127.CrossRefGoogle ScholarPubMed
Brothers, L. (1990). The social brain: A project for integrating primate behaviour and neurophysiology in a new domain. Concepts in Neuroscience, 1, 27–51.Google Scholar
Brown, J., Johnson, M. H., Paterson, S., Gilmore, S., Gsodl, M., Longhi, E., et al. (2003). Spatial representation and attention in todders with Williams syndrome and Down syndrome. Neuropsychologia, 41, 1037–1046.CrossRefGoogle ScholarPubMed
Chen, X.-N., & Korenberg, J. R. (2002). BAC resource for molecular cytogenetics. Methods in Molecular Biology, 204, 391–403.Google ScholarPubMed
Cicchetti, D. (1990). A historical perspective on the discipline of developmental psychopathology. In Rolf, J., Masten, A., Cicchetti, D., Nuechterlein, K., & Weintraub, S. (Eds.), Risk and protective factors in the development of psychopathology (pp. 2–28). New York: Cambridge University Press.CrossRefGoogle Scholar
Cicchetti, D. (2002). The impact of social experience on neurobiological systems: Illustration from a constructivist view of child maltreatment. Cognitive Development, 17, 113–142.CrossRefGoogle Scholar
Cicchetti, D. (2006). Development and psychopathology. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology: Vol. 1. Theory and method (2nd ed., pp. 1–23). New York: Wiley.Google Scholar
Cicchetti, D., & Aber, J. L. (1998). Contextualism and developmental psychopathology. Development and Psychopathology, 10, 137–141.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Blender, J. A. (2004). A multiple-levels-of-analysis approach to the study of developmental processes in maltreated children. Proceedings of the National Academy of Sciences of the United States of America, 101, 17325–17326.CrossRefGoogle Scholar
Cicchetti, D., & Dawson, G. (2002). Multiple levels of analysis. Development and Psychopathology, 14, 417–420.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Rogosch, F. (1996). Equifinality and multifinality in developmental psychopathology. Development and Psychopathology, 8, 597–600.CrossRefGoogle Scholar
Cicchetti, D., & Tucker, D. (1994). Development and self-regulatory structures of the mind. Development and Psychopathology, 6, 533–549.CrossRefGoogle Scholar
Curtis, W. J., & Cicchetti, D. (2003). Moving research on resilience into the 21st century: Theoretical and methodological considerations in examining the biological contributions to resilience. Development and Psychopathology, 15, 773–810.CrossRefGoogle Scholar
Doyle, T. F., Bellugi, U., Korenberg, J. R., & Graham, J. (2004). “Everybody in the world is my friend.” Hypersociability in young children with Williams syndrome. American Journal of Medical Genetics, 124A, 263–273.CrossRefGoogle ScholarPubMed
Doyle, T. F., Bellugi, U., Reiss, A. L., Galaburda, A. M, Mills, D. L., & Korenberg, J. R. (2004). Genes, neural systems, and cognition: Social behavior of children with Williams syndrome: Observing genes at play? [Abstract]. In Society for Neuroscience 34th Annual Meeting Abstracts. Washington, DC: Society for Neuroscience.Google Scholar
Dunn, L. M., & Dunn, L. M. (1981). Peabody Picture Vocabulary Test—Revised. Circle Pines, MN: American Guidance Service.Google Scholar
Dykens, E. M. (2003). Anxiety, fears, and phobias in persons with Williams syndrome. Developmental Neuropsychology, 23, 291–316.CrossRefGoogle ScholarPubMed
Eckert, M. A., Galaburda, A. M., Karchemskiy, A., Liang, A., Thompson, P., Dutton, R. A., et al. (2006). Anomalous Sylvian fissure morphology in Williams syndrome. NeuroImage, 33, 39–45.CrossRefGoogle ScholarPubMed
Eckert, M. A., Hu, D., Eliez, S., Bellugi, U., Galaburda, A., Korenberg, J. R., et al. (2005). Evidence for superior parietal impairment in Williams syndrome. Neurology, 64, 152–153.CrossRefGoogle ScholarPubMed
Eckert, M. A., Tenforde, A., Galaburda, A. M., Bellugi, U., Korenberg, J. R., Mills, D., et al. (2006). To modulate or not to modulate? Differing results in uniquely shaped Williams syndrome brains. NeuroImage, 32, 1001–1007.CrossRefGoogle ScholarPubMed
Einfeld, S. L., Tonge, B. J., & Florio, T. (1997). Behavioral and emotional disturbance in individuals with Williams syndrome. American Journal of Mental Retardation, 102, 45–53.2.0.CO;2>CrossRefGoogle ScholarPubMed
Elliott, C. D. (1990). Differential Abilities Scales. New York: Psychological Corporation.Google Scholar
Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., et al. (1993). Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nature Genetics, 5, 11–16.CrossRefGoogle Scholar
Farran, E. K., & Jarrold, C. (2003). Visuo-spatial cognition in Williams syndrome: Reviewing and accounting for strengths and weaknesses in performance. Developmental Neuropsychology, 23, 173–200.CrossRefGoogle Scholar
Farran, E. K., Jarrold, C., & Gathercole, S. E. (2001). Block design performance in the Williams syndrome phenotype: A problem with mental imagery? Journal of Child Psychology and Psychiatry, 42, 719–728.CrossRefGoogle ScholarPubMed
Farran, E. K., Jarrold, C., & Gathercole, S. E. (2003). Divided attention, selective attention and drawing: Processing preferences in Williams syndrome are dependent on the task administered. Neuropsychologia, 41, 676–687.CrossRefGoogle ScholarPubMed
Frigerio, E., Burt, D. M., Gagliardi, C., Cioffi, G., Martelli, S., Perrett, D. I., et al. (2006). Is everybody always my friend? Perception of approachability in Williams syndrome. Neuropsychologia, 44, 254–259.CrossRefGoogle ScholarPubMed
Gagliardi, C., Frigerio, E., Burt, D. M., Cazzaniga, I., Perrett, D. I., & Borgatti, R. (2003). Facial expression recognition in Williams syndrome. Neuropsychologia, 41, 733–738.CrossRefGoogle ScholarPubMed
Galaburda, A. M, & Bellugi, U. (2000). V. Multi-level analysis of cortical neuroanatomy in Williams syndrome. Journal of Cognitive Neuroscience, 12(Suppl. 1), 74–88.CrossRefGoogle ScholarPubMed
Galaburda, A. M., Holinger, D. P., Bellugi, U., & Sherman, G. F. (2002). Williams syndrome: Neuronal size and neuronal-packing density in primary visual cortex. Archives of Neurology, 59, 1461–1467.CrossRefGoogle ScholarPubMed
Galaburda, A. M., Wang, P. P., Bellugi, U., & Rossen, M. (1994). Cytoarchitectonic anomalies in a genetically based disorder: Williams syndrome. NeuroReport, 21, 753–757.CrossRefGoogle Scholar
Ghashghaei, H. T., & Barbas, H. (2002). Pathways to emotion: Interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey. Neuroscience, 115, 1261–1279.CrossRefGoogle ScholarPubMed
Goldman-Rakic, P. (1987). Development of cortical circuitry and cognitve function. Child Development, 58, 601–622.CrossRefGoogle Scholar
Goldsmith, H. H., Reilly, J., Lemery, K. S., Longley, S., & Prescott, A. (1993). Preschool Laboratory Temperament Assessment Battery (PS Lab-TAB; Version 1.0. Technical Report). Madison, WI: University of Wisconsin–Madison, Department of Psychology.Google Scholar
Gosch, A., & Pankau, R. (1994). Social–emotional and behavioral adjustment in children with Williams–Beuren syndrome. American Journal of Medical Genetics, 53, 335–339.CrossRefGoogle ScholarPubMed
Gosch, A., & Pankau, R. (1997). Personality characteristics and behavioral problems in individuals of different ages with Williams syndrome. Developmental Medicine and Child Neurology, 39, 327–533.CrossRefGoogle Scholar
Gray, V., Karmiloff-Smith, A., Funnell, E., & Tassabehji, M. (2006). In-depth analysis of spatial cognition in Williams syndrome: A critical assessment of the role of the LIMK1 gene. Neuropsychologia, 44, 679–685.CrossRefGoogle ScholarPubMed
Grossman, A. W., Churchill, J. D., McKinney, B. C., Kodish, I. M., Otte, S. L., & Greenough, W. T. (2003). Experience effects on brain development: Possible contributions to psychopathology. Journal of Child Psychology and Psychiatry, 44, 33–63.CrossRefGoogle ScholarPubMed
Harrison, D., Reilly, J. S., & Klima, E. S. (1995). Unusual social behavior in Williams syndrome: Evidence from biographical interviews. Genetic Counseling, 6, 181–183.Google Scholar
Hirota, H., Matsuoka, R., Chen, X.-N., Salandanan, L. S., Lincoln, A., Rose, F. E., et al. (2003). Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Genetics in Medicine, 5, 311–321.CrossRefGoogle ScholarPubMed
Holinger, D. P., Bellugi, U., Mills, D. L., Korenberg, J. R., Reiss, A. L., Sherman, G. F., et al. (2005). Relative sparing of primary auditory cortex in Williams syndrome. Brain Research, 1037, 35–42.CrossRefGoogle ScholarPubMed
Hoogenraad, C. C., Eussen, B. H., Langeveld, A., van Haperen, R., Winterberg, S., Wouters, C. H., et al. (1998). The murine CYLN2 gene: Genomic organization, chromosome localization, and comparison to the human gene that is located within the 7q11.23 Williams syndrome critical region. Genomics, 53, 348–358.CrossRefGoogle Scholar
Howlin, P., Davies, M., & Udwin, O. (1998). Cognitive functioning in adults with Williams syndrome. Journal of Child Psychology and Psychiatry, 39, 183–189.CrossRefGoogle ScholarPubMed
Jackowski, A. P., & Schultz, R. T. (2005). Foreshortened dorsal extension of the central sulcus in Williams syndrome. Cortex, 41, 282–290.CrossRefGoogle ScholarPubMed
Järvinen-Pasley, A., Reilly, J., Reiss, A. L., Korenberg, J. R., & Bellugi, U. (2006). Investigating the relative strengths of social–perceptual abilities and expressive social behaviors in Williams syndrome. Poster presented at the Cognitive Neuroscience Society's Annual Conference, San Francisco, CA.Google Scholar
Johnson, M. H. (2001). Functional brain development in humans. Nature Reviews Neuroscience, 2, 475–483.CrossRefGoogle ScholarPubMed
Johnston, M. V. (2001). Developmental disorders of activity dependent neuronal plasticity. Indian Journal of Pediatrics, 68, 3–426.CrossRefGoogle ScholarPubMed
Jones, W., Bellugi, U., Lai, Z., Chiles, M., Reilly, J., Lincoln, A., et al. (2000). II. Hypersociability in Williams syndrome. Journal of Cognitive Neuroscience, 12(Suppl. 1), 30–46.CrossRefGoogle ScholarPubMed
Jones, W., Hesselink, J., Courchesne, E., Duncan, T., Matsuda, K., & Bellugi, U. (2002). Cerebellar abnormalities in infants and toddlers with Williams syndrome. Developmental Medicine and Child Neurology, 44, 688–694.CrossRefGoogle ScholarPubMed
Karmiloff-Smith, A. (1992). Beyond modularity: A developmental perspective on cognitive science. Cambridge, MA: MIT Press.Google Scholar
Karmiloff-Smith, A. (1997). Crucial differences between developmental cognitive neuroscience and adult neuropsychology. Developmental Neuropsychology, 13, 513–524.CrossRefGoogle Scholar
Karmiloff-Smith, A. (1998). Development itself is the key to understanding developmental disorders. Trends in Cognitive Sciences, 2, 389–398.CrossRefGoogle ScholarPubMed
Karmiloff-Smith, A. (2006). The tortuous route from genes to behavior: A neuroconstructivist approach. Cognitive, Affective, & Behavioral Neuroscience, 6, 9–17.CrossRefGoogle Scholar
Karmiloff-Smith, A. (2007a). Atypical epigenesis. Developmental Science, 10, 84–88.CrossRefGoogle ScholarPubMed
Karmiloff-Smith, A. (2007b). Research into Williams syndrome: The state of the art. In Nelson, C. A. & Luciana, M. (Eds.) Handbook of developmental cognitive neuroscience. Cambridge, MA: MIT Press.Google Scholar
Karmiloff-Smith, A., Ansari, D., Campbell, L., Scerif, G., & Thomas, M. S. C. (2006). Theoretical implications of studying genetic disorders: The case of Williams syndrome. In Morris, C., Lenhoff, H. & Wang, P. (Eds.), Williams–Beuren syndrome: Research and clinical perspectives (pp. 254–273). Baltimore, MD: Johns Hopkins University Press.Google Scholar
Karmiloff-Smith, A., Grant, J., Ewing, S., Carette, M. J., Metcalfe, K., Donnai, D., et al. (2003). Using case study comparisons to explore genotype-phenotype correlations in Williams–Beuren syndrome. Journal of Medical Genetics, 40, 136–140.CrossRefGoogle ScholarPubMed
Karmiloff-Smith, A., Klima, E., Bellugi, U., Grant, J., & Baron-Cohen, S. (1995). Is there a social module? Language, face processing and theory of mind in individuals with Williams syndrome. Journal of Cognitive Neuroscience, 7, 196–208.CrossRefGoogle Scholar
Karmiloff-Smith, A., Scherif, G., & Thomas, M. (2002). Different approaches to relating genotype to phenotype in developmental disorders. Development and Psychopathology, 40, 311–322.CrossRefGoogle ScholarPubMed
Karmiloff-Smith, A., & Thomas, M. (2003). What can developmental disorders tell us about the neurocomputational constraints that shape development? The case of Williams syndrome. Development and Psychopathology, 15, 969–990.CrossRefGoogle ScholarPubMed
Klein-Tasman, B. P., & Mervis, C. B. (2003). Distinctive personality characteristics of 8-, 9-, and 10-year-olds with Williams syndrome. Developmental Neuropsychology, 23, 269–290.CrossRefGoogle ScholarPubMed
Korenberg, J. R., Bellugi, U., Chen, X.-N., Galaburda, Saladanan L. S., Tirosh-Wagner, A., Galaburda, A., et al. (2007, November). Genes, neural systems, and social behavior: Genetic origins of hypersociability in Williams syndrome. Poster presented at the Society for Neuroscience's Annual Conference, San Diego, CA.Google Scholar
Korenberg, J. R., Bellugi, U., Salandanan, L. S., Mills, D. L., & Reiss, A. L. (2003). Williams syndrome: A neurogenetic model of human behavior. In Encyclopedia of the human genome (pp. 756–766). London: Nature Publishing Group.Google Scholar
Korenberg, J. R., & Chen, X.-N. (2001). Understanding the molecular genetic basis of human cognition: Evidence from Williams syndrome [Abstract]. Social Neuroscience, 5, 986.Google Scholar
Korenberg, J. R., Chen, X.-N., Hirota, H., Lai, Z., Bellugi, U., Burian, D., et al. (2000). VI. Genome structure and cognitive map of Williams syndrome. Journal of Cognitive Neuroscience, 12(Suppl. 1), 89–107.CrossRefGoogle ScholarPubMed
Korenberg, J. R., Dai, L., Bellugi, U., Järvinen-Pasley, A., Mills, D. L., Galaburda, A., et al. (in press). Deletion of 7q11.23 Genes and Williams Syndrome. In Epstein, C. J., Erickson, R. P., & Wynshaw-Boris, A. (Eds.), Inborn errors of development (2nd ed.). New York: Oxford University Press.Google Scholar
Kreiter, J., Bellugi, U., Lichtenberger, E. O., Klima, E., Reilly, J., & Kikuchi, D. K. (2002). Gregarious language in narratives by adolescents Williams syndrome. Poster presented at the American Speech–Language–Hearing Association Conference, Atlanta, GA.Google Scholar
Kuhl, P. K. (2004). Early language acquisition: Cracking the speech code. Nature Reviews Neuroscience, 5, 831–843.CrossRefGoogle ScholarPubMed
Labov, W., & Waletsky, J. (1967). Narrative analysis: Oral versions of personal experience. In Helm, J. (Ed.), Essays on the verbal and visual arts (pp. 12–44). Seattle, WA: University of Washington Press.Google Scholar
LaCroix, A., Bernicot, J., & Reilly, J. (in press). Narrative and collaborative conversation in French-speaking children with Williams syndrome. Journal of Neurolinguistics.Google Scholar
Laing, E., Butterworth, G., Ansari, D., Gsödl, M., Longhi, E., Panagiotaki, G., et al. (2002). Atypical development of language and social communication in toddlers with Williams syndrome. Developmental Science, 5, 233–246.CrossRefGoogle Scholar
Lando, R., Reilly, J., Searcy, Y., & Bellugi, U. (2006). Prosody use in adolescents with Williams syndrome. Poster presented at the Williams Syndrome Association Professional Conference in Richmond, VA, July 2006.Google Scholar
Laws, G., & Bishop, D. M. V. (2004). Pragmatic language impairment and social deficits in Williams syndrome: A comparison with Down's syndrome and specific language impairment. International Journal of Language and Communication Disorders, 39, 45–64.CrossRefGoogle ScholarPubMed
LeDoux, J. (2003). The emotional brain, fear, and the amygdala. Cellular and Molecular Neurobiology, 23, 727–738.CrossRefGoogle ScholarPubMed
Leyfer, O. T., Woodruff-Borden, J., Klein-Tasman, B. P., Fricke, J. S., & Mervis, C. B. (2006). Prevalence of psychiatric disorders in 4 to 16-year-olds with Williams syndrome. American Journal of Medical Genetics B: Neuropsychiatric Genetics, 141, 615–622.CrossRefGoogle Scholar
Losh, M., Bellugi, U., Reilly, J., & Anderson, D. (2000). Narrative as a social engagement tool: The excessive use of evaluation in narratives from children with Williams syndrome. Narrative Inquiry, 10, 1–26.CrossRefGoogle Scholar
Lowery, M. C., Morris, C. A., Ewart, A., Brothman, L. J., Zhu, X. L., Leonard, C. O., et al. (1995). Strong correlation of elastin deletions, detected by FISH, with Williams syndrome. American Journal of Human Genetics, 57, 49–53.Google ScholarPubMed
Majdan, M., & Schatz, C. J. (2006). Effects of visual experience on activity-dependent gene regulation in cortex. Nature Neuroscience, 9, 650–659.CrossRefGoogle ScholarPubMed
Masataka, N. (2001). Why early linguistic milestones are delayed in children with Williams syndrome: Late onset of hand banging as a possible rate-limiting constraint on the emergence on canonical babbling. Developmental Science, 4, 158–164.CrossRefGoogle Scholar
Mayer, M. (1969). Frog, where are you? New York: Dial Books for Young Readers.Google Scholar
Meng, Y., Zhang, Y., Tregoubov, V., Janus, C., Cruz, L., Jackson, M., et al. (2002). Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron, 35, 121–133.CrossRefGoogle ScholarPubMed
Mervis, C. B., & Bertrand, J. (1994). Acquisition of the novel nameless category (N3C) principle. Child Development, 65, 1646–1662.CrossRefGoogle ScholarPubMed
Mervis, C. B., & Bertrand, J. (1997). Developmental relations between cognition and language. In Adamson, L. B. & Romski, M. A. (Eds.), Communication and language acquisition: Discoveries from atypical development. Baltimore, MD: Paul Brookes.Google Scholar
Mervis, C. B., & Klein-Tasman, B. P. (2000). Williams syndrome: Cognition, personality, and adaptive behavior. Mental Retardation and Developmental Disabilities Research Reviews, 6, 148–158.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Mervis, C. B., Morris, C. A., Klein-Tasman, B. P., Bertrand, J., Kwitny, S., Appelbaum, G., et al. (2003). Attentional characteristics of infants and toddlers with Williams syndrome during triadic interactions. Developmental Neuropsychology, 23, 243–268.CrossRefGoogle ScholarPubMed
Mervis, C. B., & Robinson, B. F. (2000). Expressive vocabulary ability of toddlers with Williams syndrome or Down syndrome: A comparison. Developmental Neuropsychology, 17, 111–126.CrossRefGoogle ScholarPubMed
Mervis, C. B., Robinson, B. F., Bertrand, J., Morris, C. A., Klein-Tasman, B. P., & Armstrong, S. C. (2000). The Williams syndrome cognitive profile. Brain and Cognition, 44, 604–628.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, A., Hariri, A. R., Munoz, K. E., Mervis, C. B., Mattay, V. S., Morris, C. A., & Berman, K. F. (2005). Neural correlates of genetically abnormal social cognition in Williams syndrome. Nature Neuroscience, 8, 991–993.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, A., Kohn, P., Mervis, C. B., Kippenhan, J. S., Olsen, R. K., Morris, C. A., et al. (2004). Neural basis of genetically determined visuospatial construction deficit in Williams syndrome. Neuron, 43, 623–631.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, A., Mervis, C. B., & Berman, K. F. (2006). Neural mechanisms in Williams syndrome: A unique window to genetic influences on cognition and behaviour. Nature Reviews Neuroscience, 7, 380–393.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, A., Mervis, C. B., Sarpal, D., Koch, P., Steele, S., Kohn, P., et al. (2005). Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome. Journal of Clinical Investigation, 115, 1888–1895.CrossRefGoogle ScholarPubMed
Mills, D., Alvarez, T., St. George, M., Appelbaum, L., Bellugi, U., & Neville, H. (2000). Electrophysiological studies of face processing in Williams syndrome. Journal of Cognitive Neuroscience, 12(Suppl. 1), 47–64.CrossRefGoogle ScholarPubMed
Mills, D., Yam, A., Lincoln, A., Rull, D., Galaburda, A., Bellugi, U., et al. (2007). Autism and Williams syndrome: Contrasting patterns of social brain activity. Manuscript submitted for publication.Google Scholar
Mobbs, D., Garrett, A. S., Menon, V., Rose, F. E., Bellugi, U., & Reiss, A. L. (2004). Anomalous brain activation during face and gaze processing in Williams syndrome. Neurology, 62, 2070–2076.CrossRefGoogle ScholarPubMed
Morris, C. A., Demsey, S. A., Leonard, C. O., Dilts, C., & Blackburn, B. L. (1988). Natural history of Williams syndrome: Physical characteristics. Journal of Pediatrics, 113, 318–326.CrossRefGoogle ScholarPubMed
Morris, C. A., & Mervis, C. B. (2000). Williams syndrome and related disorders. Annual Review of Genomics and Human Genetics, 1, 461–484.CrossRefGoogle ScholarPubMed
Morris, C. A., Mervis, C. B., Hobart, H. H., Gregg, R. G., Bertrand, J., Ensing, G. J., et al. (2003). GTF2I hemizygosity implicated in mental retardation in Williams syndrome: Genotype–phenotype analysis of five families with deletions in the Williams syndrome region. American Journal of Medical Genetics A, 123, 45–59.CrossRefGoogle Scholar
Nazzi, T., Paterson, S., & Karmiloff-Smith, A. (2003). Early word segmentation by infants and toddlers with Williams syndrome. Infancy, 4, 251–271.CrossRefGoogle Scholar
Noldus, L. P., Trienes, R. J., Hendriksen, A. H., Jansen, H., & Jansen, R. G. (2000). The observer video-pro: New software for the collection, management, and presentation of time-structured data from videotapes and digital media files. Behavior Research Methods, Instruments, & Computers, 32, 197–206.CrossRefGoogle ScholarPubMed
Paterson, S. J., Girelli, L., Butterworth, B., & Karmiloff-Smith, A. (2006). Are numerical impairments syndrome specific? Evidence from Williams syndrome and Down syndrome. Journal of Child Psychology and Psychiatry, 47, 190–204.CrossRefGoogle Scholar
Phillips, M. L., Young, A. W., Senior, C., Brammer, M., Andrew, C., Calder, A. J., et al. (1997). A specific neural substrate for perceiving facial expressions of disgust. Nature, 389, 495–498.CrossRefGoogle ScholarPubMed
Pinker, S. (1994). The language instinct. New York: Harper Perennial.CrossRefGoogle Scholar
Pinker, S. (1999). Words and rules. London: Weidenfeld & Nicolson.Google Scholar
Plesa-Skwerer, D., Faja, S., Schofield, C., Verbalis, A., & Tager-Flusberg, H. (2006). Perceiving facial and vocal expressions of emotion in individuals with Williams syndrome. American Journal of Mental Retardation, 111, 15–26.CrossRefGoogle ScholarPubMed
Plesa-Skwerer, D., Verbalis, A., Schofield, C., Faja, S., & Tager-Flusberg, H. (2005). Social-perceptual abilities in adolescents and adults with Williams syndrome. Cognitive Neuropsychology, 22, 1–12.Google Scholar
Plomin, R., & Rende, R. (1991). Human behavior genetics. Annual Review of Psychology, 42, 161–190.CrossRefGoogle Scholar
Posner, M. I., Rothbart, M. K., Farah, M., & Bruer, J. (2001). The developing brain. Developmental Science, 4, 253–387.Google Scholar
Price, J. L. (1999). Prefrontal cortical networks related to visceral function and mood. Annals of the New York Academy of Sciences, 877, 383–396.CrossRefGoogle ScholarPubMed
Proschel, C., Blouin, M. J., Gutowski, N. J., Ludwig, R., & Noble, M. (1995). Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro. Oncogene, 11, 1271–1281.Google Scholar
Rae, C., Karmiloff-Smith, A., Lee, M. A., Dixon, R. M., Blamire, A. M., Thompson, C. H., et al. (1998). Brain biochemistry in Williams syndrome: Evidence for a role of the cerebellum in cognition? Neurology, 51, 33–40.CrossRefGoogle ScholarPubMed
Reilly, J., Bernicot, J., Vicari, S., LaCroix, A., & Bellugi, U. (2005). Narratives in children with Williams syndrome: A cross linguistic perspective. In Ravid, D. & Shyldkrot, H. B. Z. (Eds.), Perspectives on language and language development: Essays in honor of Ruth A. Berman (pp. 303–312). Dordrecht: Kluwer.CrossRefGoogle Scholar
Reilly, J., Klima, E. S., & Bellugi, U. (1990). Once more with feeling: Affect and language in atypical populations. Development and Psychopathology, 2, 367–391.CrossRefGoogle Scholar
Reilly, J., LaCroix, A., Poirier, J., Bernicot, J., Bellugi, U., & Klima, E. (2005). Narratives in French and American children with Williams syndrome. Le Langage et L'Homme: Logopedie, Psychologie, Audiologie.Google Scholar
Reilly, J., Losh, M., Bellugi, U., & Wulfeck, B. (2004). Frog, where are you? Narratives in children with specific language impairment, early focal brain injury, and Williams syndrome. Brain and Language, 88, 229–247.CrossRefGoogle ScholarPubMed
Reiss, A. L., & Dant, C. C. (2003). The behavioral neurogenetics of fragile X syndrome: Analyzing gene–brain–behavior relationships in child developmental pathologies. Development and Psychopathology, 15, 927–968.CrossRefGoogle Scholar
Reiss, A. L., Eckert, M. A., Rose, F. E., Karchemskiy, A., Kesler, S., Chang, M., et al. (2004). An experiment of nature: Brain anatomy parallels cognition and behavior in Williams syndrome. Journal of Neuroscience, 24, 5009–5015.CrossRefGoogle ScholarPubMed
Reiss, A. L., Eliez, S., Schmitt, J. E., Patwardhan, A., & Haberecht, M. (2000). Brain imaging in neurogenetic conditions: Realizing the potential of behavioral neurogenetics research. Mental Retardation and Developmental Disability Research Reviews, 6, 186–197.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Reiss, A., Eliez, S., Schmitt, E., Straus, E., Lai, Z., Jones, W., et al. (2000). Neuroanatomy of Williams syndrome: A high-resolution MRI study. Journal of Cognitive Neuroscience, 12(Suppl. 1), 65–73.CrossRefGoogle ScholarPubMed
Richters, J. E. (1997). The Hubble hypothesis and the developmentalist's dilemma. Development and Psychopathology, 9, 193–199.CrossRefGoogle ScholarPubMed
Rolls, E. T., Hornak, J., Wade, D., & McGrath, J. (1994). Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 1518–1524.CrossRefGoogle ScholarPubMed
Rossen, M. L., Jones, W., Wang, P. P., & Klima, E. S. (1996). Face processing: Remarkable sparing in Williams syndrome. Genetic Counseling, 6, 138–140.Google Scholar
Rothbart, M. K., Ahadi, S. A., Hershey, K. L., & Fisher, P. (2001). Investigations of temperament at three to seven years: The Children's Behavior Questionnaire. Child Development, 72, 1394–1408.CrossRefGoogle ScholarPubMed
Rutter, M., & Sroufe, L. A. (2000). Developmental psychopathology: Concepts and challenges. Development and Psychopathology, 12, 265–296.CrossRefGoogle ScholarPubMed
Scerif, G., & Karmiloff-Smith, A. (2005). The dawn of cognitive genetics? Crucial developmental caveats. Trends in Cognitive Sciences, 9, 126–135.CrossRefGoogle ScholarPubMed
Schmitt, J. E., Eliez, S., Warsofsky, I. S., Bellugi, U., & Reiss, A. L. (2001). Corpus callosum morphology in Williams syndrome: Relation to genetics and behavior. Developmental Medicine and Child Neurology, 43, 155–159.CrossRefGoogle ScholarPubMed
Schmitt, J. E., Watts, K., Eliez, S., Bellugi, U., Galaburda, A., & Reiss, A. L. (2002). Increased gyrification in Williams syndrome: Evidence using 3D MRI methods. Developmental Medicine and Child Neurology, 44, 292–295.CrossRefGoogle ScholarPubMed
Singer-Harris, N. G., Bellugi, U., Bates, E., Jones, W., & Rossen, M. (1997). Contrasting profiles of language development in children with Williams and Down syndromes. Developmental Neuropsychology, 13, 345–370.CrossRefGoogle Scholar
Strømme, P., Bjørnstad, P. G., & Ramstad, K. (2002). Prevalence estimation of Williams syndrome. Journal of Child Neurology, 17, 269–271.CrossRefGoogle ScholarPubMed
Sullivan, K., & Tager-Flusberg, H. (1999). Second-order belief attribution in Williams syndrome: Intact or impaired? American Journal of Mental Retardation, 104, 523–532.2.0.CO;2>CrossRefGoogle ScholarPubMed
Tager-Flusberg, H., Boshart, J., & Baron-Cohen, S. (1998). Reading the windows to the soul: Evidence of domain-specific sparing in Williams syndrome. Journal of Cognitive Neuroscience, 10, 631–639.CrossRefGoogle Scholar
Tager-Flusberg, H., & Sullivan, K. (2000). A componential view of theory of mind: Evidence from Williams syndrome. Cognition, 76, 59–89.CrossRefGoogle ScholarPubMed
Tanaka, J. W., & Farah, M. J. (1993). Parts and wholes in face recognition. Quarterly Journal of Experimental Psychology, 46A, 225–245.CrossRefGoogle Scholar
Tassabehji, M. (2003). Williams–Beuren syndrome: A challenge for genotype-phenotype correlations. Human Molecular Genetics, 12, R229–R237.CrossRefGoogle ScholarPubMed
Tassabehji, M., Hammond, P., Karmiloff-Smith, A., Thompson, P., Thorgeirsson, S. S., Durkin, M. E., et al. (2005). GTF2IRD1 in craniofacial development of humans and mice. Science, 310, 1184–1187.CrossRefGoogle ScholarPubMed
Tassabehji, M., Metcalfe, K., Karmiloff-Smith, A., Carette, M. J., Grant, J., Dennis, N., et al. (1999). Williams syndrome: Use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. American Journal of Human Genetics, 64, 118–125.CrossRefGoogle ScholarPubMed
Tellegen, A. (1985). Structures of mood and personality and their relevance to assessing anxiety, with an emphasis on self-report. In Tuma, A. H. & Masser, J. D. (Eds.), Anxiety and the anxiety disorders (pp. 681–716). Hillsdale, NJ: Erlbaum.Google Scholar
Thompson, P. M., Lee, A. D., Dutton, R. A., Geaga, J. A., Hayashi, K. M., Eckert, M. A., et al. (2005). Abnormal cortical complexity and thickness profiles mapped in Williams syndrome. Journal of Neuroscience, 25, 4146–4158.CrossRefGoogle ScholarPubMed
Tomaiuolo, F., Di Paola, M., Caravale, B., Vicari, S., Petrides, M., & Caltagirone, C. (2002). Morphology and morphometry of the corpus callosum in Williams syndrome: A T1-weighted MRI study. NeuroReport, 13, 2281–2284.CrossRefGoogle ScholarPubMed
Udwin, O., & Yule, W. (1990). Expressive language of children with Williams syndrome. American Journal of Medical Genetics, 6(Suppl.), 108–114.Google ScholarPubMed
Udwin, O., & Yule, W. (1991). A cognitive and behavioural phenotype in Williams syndrome. Journal of Clinical Experimental Neuropsychology, 13, 232–244.CrossRefGoogle ScholarPubMed
von Arnim, G. & Engel, P. (1964). Mental retardation related to hypercalcaemia. Developmental Medicine and Child Neurology, 6, 366–377.CrossRefGoogle Scholar
Weisz, J. R., Weiss, B., Alicke, M. D., & Klotz, M. L. (1987). Effectiveness of psychotherapy with children and adolescents: A meta-analysis for clinicians. Journal of Consulting and Clinical Psychology, 55, 542–549.CrossRefGoogle ScholarPubMed
Williams, J. C., Barratt-Boyes, B. G., & Lowe, J. B. (1961). Supravalvular aortic stenosis. Circulation, 24, 1311–1318.CrossRefGoogle ScholarPubMed
Young, E. J., Lipina, T., Tam, E., Mandel, A., Clapcote, S. J., Bechard, A. R., et al. (in press). Reduced fear and aggression and altered serotonin metabolism in Gtf2ird1-targeted mice. Genes, Brain and Behavior.Google Scholar
Zhao, C., Aviles, C., Abel, R. A., Almli, C. R., McQuillen, P., & Pleasure, S. J. (2005). Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Development, 132, 2917–2927.CrossRefGoogle ScholarPubMed
Zitzer-Comfort, C., Doyle, T. F., Masataka, N., Korenberg, J. R., & Bellugi, U. (2007). Nature and nurture: Williams syndrome across cultures. Developmental Science, 10, 755–762.CrossRefGoogle Scholar