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.

Genetic contributions to human cognition and behavior are clear but difficult to define. Williams syndrome (WS) provides a unique model for relating single genes to visual-spatial cognition and social behavior. We defined a ~1.5 Mb region of ~25 genes deleted in >98% of typical WS and then rare small deletions, showing that visual-spatial construction (VSC) in WS was associated with the genes GTF2IRD1 and GTF2I. To distinguish the roles of GTF2IRD1 and GTF2I in VSC and social behavior, we utilized multiple genomic methods (custom high resolution oligonucleotide microarray, multicolor FISH and somatic cell hybrids analyzed by PCR) to identify individuals deleted for either gene but not both. We analyzed genetic, cognitive and social behavior in a unique individual with WS features (heart defects, small size, facies), but with an atypical deletion of a set of genes that includes GTF2IRD1, but not GTF2I. The centromeric breakpoint localized to the region 72.32-72.38Mb and the telomeric breakpoint to 72.66 Mb, 10kb downstream of GTF2IRD1. Cognitive testing (WPPSI-R, K-BIT, and PLS-3) deomstrated striking deficits in VSC (Block Design, Object Assembly) but overall performance 1.5-3 SD above WS means. We have now integrated the genetic, clinical and cognitive data with previous reports of social behavior in this subject. These results combine with previous data from small deletions to suggest the gene GTF2IRD1 is associated with WS facies and VSC, and that GTF2I may contribute to WS social behaviors including increased gaze and attention to strangers.

Prosody can be conceived as having form (auditory-perceptual characteristics) and function (pragmatic/linguistic meaning). No known studies have examined the relationship between form-and functionlevel prosodic skills in relation to the effects of stimulus length and/or complexity upon such abilities in autism. Research in this area is both insubstantial and inconclusive. Children with autism and controls completed the receptive tasks of the Profiling Elements of Prosodic Systems in Children (PEPS-C) test, which examines both form-and function-level skills, and a sentence-level task assessing the understanding of intonation. While children with autism were unimpaired in both form and function tasks at the single-word level, they showed significantly poorer performance in the corresponding sentence-level tasks than controls. Implications for future research are discussed.

Theories of autism have proposed that a bias towards low-level perceptual information, or a featural/surface-biased information-processing style, may compromise higher-level language processing in such individuals. Two experiments, utilizing linguistic stimuli with competing low-level/perceptual and high-level/semantic information, tested processing biases in children with autism and matched controls. Whereas children with autism exhibited superior perceptual processing of speech relative to controls, and showed no evidence of either a perceptual or semantic processing bias, controls showed a tendency to process speech semantically. The data provide partial support to the perceptual theories of autism. It is additionally proposed that the pattern of results may reflect different patterns of attentional focusing towards single or multiple stimulus cues in speech between children with autism and controls.