Development and Psychopathology

Research Article

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

Anna Järvinen-Pasleya1, Ursula Bellugia1 c1, Judy Reillya2a3, Debra L. MILLSa4, Albert Galaburdaa5, Allan L. Reissa6 and Julie R. Korenberga7

a1 Salk Institute for Biological Studies

a2 San Diego State University

a3 University of Poitiers, France

a4 Emory University

a5 Beth Israel Deaconess Medical Center

a6 Stanford University School of Medicine

a7 Cedars-Sinai Medical Center


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.


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.).