Williams syndrome: cognition, personality, and adaptive behavior

Williams syndrome is caused by a microdeletion of at least 16 genes on chromosome 7q11.23. The syndrome results in mild to moderate mental retardation or learning disability. The behavioral phenotype for Williams syndrome is characterized by a distinctive cognitive profile and an unusual personality profile. Relative to overall level of intellectual ability, individuals with Williams syndrome typically show a clear strength in auditory rote memory, a strength in language, and an extreme weakness in visuospatial construction. The personality of individuals with Williams syndrome involves high sociability, overfriendliness, and empathy, with an undercurrent of anxiety related to social situations. The adaptive behavior profile for Williams syndrome involves clear strength in socialization skills (especially interpersonal skills related to initiating social interaction), strength in communication, and clear weakness in daily living skills and motor skills, relative to overall level of adaptive behavior functioning. Literature relevant to each of the components of the Williams syndrome behavioral phenotype is reviewed, including operationalizations of the Williams syndrome cognitive profile and the Williams syndrome personality profile. The sensitivity and specificity of these profiles for Williams syndrome, relative to individuals with other syndromes or mental retardation or borderline normal intelligence of unknown etiology, is considered. The adaptive behavior profile is discussed in relation to the cognitive and personality profiles. The importance of operationalizations of crucial components of the behavioral phenotype for the study of genotype/phenotype correlations in Williams syndrome is stressed. MRDD Research Reviews 2000;6:148-158.     

Short-Term Memory Deficits Are Not Uniform in Down and Williams Syndromes

Neuropsychological investigation of the development of the mnesic function in mental retardation has primarily focused on evaluating short-term memory (STM). Studies have often documented a reduced verbal short-term memory span in individuals with mental retardation and with Down syndrome in particular, compared to groups of mental age-matched controls. However, recent evidence suggests that verbal short-term memory is not equally impaired in all individuals with mental retardation. Findings in children with Williams syndrome are particularly relevant in this regard. Also, data concerning STM for visual information suggest that visual-object and visual-spatial working memory may be differently compromised in people with mental retardation. In particular, individuals with Williams syndrome exhibit specific difficulties in visual-spatial but not in visual-object working memory tasks compared to typically-developing children matched for mental age. Instead, people with Down syndrome show reduced performance in both visual-spatial and visual-object tests. Taken together, these results reinforce the view that intellectual disability is not a unitary condition characterized by homogeneous slowness of cognitive development but a variety of conditions in which some cognitive functions may be more disrupted than others. The finding that the working memory deficit in individuals with Williams and Down syndrome may be qualitatively differentiated also supports the hypothesis that it is not simply a manifestation of general cognitive impairment but, rather, the expression of a specific deficit of a discrete cognitive ability.     

Global Spatial Organization by Individuals with Williams Syndrome

Williams syndrome is a genetically determined disorder with a characteristic cognitive profile. Overall IQ tends to be lower than in the normally developing population, performance on measures of linguistic ability is somewhat higher than would be expected given the levels of IQ typical for this group, and there is a particular weakness in visuospatial construction (e.g., block design tasks). A well-known hypothesis about the deficit in visuospatial construction is that people with Williams syndrome are strongly inclined to be local spatial processors. We report a test of this hypothesis that used a visual search task sensitive to spontaneous global spatial organization. A sample of adults with Williams syndrome produced a pattern of data demonstrating that they spontaneously organize spatial displays at a global level. Indeed, individuals with Williams syndrome found it more difficult to change from global to local processing than participants with normal intelligence. We suggest that the primary problem with visuospatial construction in people with Williams syndrome is not in the salience of single levels of organization but rather in the difficulty of changing between organizations.     

Language and communicative development in Williams syndrome

Williams syndrome, a genetic disorder caused by a microdeletion of approximately 25 genes on chromosome 7q11.23, is associated with mild to moderate intellectual disability or learning difficulties. Most individuals with Williams syndrome evidence a cognitive profile including relative strengths in verbal short-term memory and language, and considerable weakness in visuospatial construction. The syndrome has often been argued to provide strong evidence for the independence of language from other aspects of cognition. We provide a brief history of early research on the language abilities of individuals with Williams syndrome and then review contemporary studies of language and cognition in Williams syndrome, beginning with a consideration of performance on standardized assessments. In the remainder of the article, we first consider early language acquisition, with a focus on speech production and perception, vocabulary acquisition, and communicative/pragmatic development and then consider the language abilities of school-age children and adolescents, focusing on semantics, grammar, and pragmatics. We argue that rather than being the paradigm case for the independence of language from cognition, Williams syndrome provides strong evidence of the interdependence of many aspects of language and cognition.     

Linguistic Profile of Individuals with Down Syndrome: Comparing the Linguistic Performance of Three Developmental Disorders

An increasing number of studies, addressing the linguistic abilities of individuals with Down syndrome (DS) suggest that they exhibit strengths and weaknesses within the linguistic domain. This article critically reviews the literature on the linguistic profile of individuals with DS, with particular emphasis on the expression and reception of vocabulary and grammar, including nonverbal linguistic expression during infant development. In doing so, attention is given to recent comparative studies of the linguistic abilities of individuals with DS, Specific Language Impairment (SLI), and Williams syndrome (WS). The possibility that deficits in one cognitive system may have consequences in another cognitive system, and that these consequences may define the nature of the impairment in each clinical syndrome is further discussed with suggestions for future research.     

Linguistic profile of individuals with Down syndrome: comparing the linguistic performance of three developmental disorders.

An increasing number of studies, addressing the linguistic abilities of individuals with Down syndrome (DS) suggest that they exhibit strengths and weaknesses within the linguistic domain. This article critically reviews the literature on the linguistic profile of individuals with DS, with particular emphasis on the expression and reception of vocabulary and grammar, including nonverbal linguistic expression during infant development. In doing so, attention is given to recent comparative studies of the linguistic abilities of individuals with DS, Specific Language Impairment (SLI), and Williams syndrome (WS). The possibility that deficits in one cognitive system may have consequences in another cognitive system, and that these consequences may define the nature of the impairment in each clinical syndrome is further discussed with suggestions for future research.     

Williams syndrome: a genetic deletion disorder presenting clues to the biology of sociability and clinical challenges of hypersociability

Williams syndrome is a neurodevelopmental disorder that results from the deletion of approximately 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. Furthermore, 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 neuropsychiatric 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.     

Multiple object tracking in people with Williams syndrome and in normally developing children

Multiple object tracking is hypothesized to utilize visual indexes, which may provide rapid, parallel access to a limited number of visual objects, thereby supporting a variety of spatial tasks. We examined whether faulty indexing might play a role in the severe visuospatial deficits found in Williams syndrome. We asked observers to track from one to four targets in a display of eight identical objects. Objects remained stationary (static condition) or moved randomly and independently (moving condition) for 6 s, after which observers pointed to the objects they thought were targets. People with Williams syndrome were impaired in the moving condition, but not the static condition, compared with mental-age-matched control participants. Normal children who were younger than the mental-age-matched control children did not show the same profile as individuals with Williams syndrome, which suggests that the difference between the tasks in Williams syndrome did not reflect simple developmental immaturity. Error analysis revealed that all groups had "slippery" indexes, falsely identifying target neighbors, and further suggested that people with Williams syndrome deploy fewer indexes than do people without this disorder.     

Facial emotion recognition in Williams syndrome and Down syndrome: A matching and developmental study

In this study both the matching and developmental trajectories approaches were used to clarify questions that remain open in the literature on facial emotion recognition in Williams syndrome (WS) and Down syndrome (DS). The matching approach showed that individuals with WS or DS exhibit neither proficiency for the expression of happiness nor specific impairments for negative emotions. Instead, they present the same pattern of emotion recognition as typically developing (TD) individuals. Thus, the better performance on the recognition of positive compared to negative emotions usually reported in WS and DS is not specific of these populations but seems to represent a typical pattern. Prior studies based on the matching approach suggested that the development of facial emotion recognition is delayed in WS and atypical in DS. Nevertheless, and even though performance levels were lower in DS than in WS, the developmental trajectories approach used in this study evidenced that not only individuals with DS but also those with WS present atypical development in facial emotion recognition. Unlike in the TD participants, where developmental changes were observed along with age, in the WS and DS groups, the development of facial emotion recognition was static. Both individuals with WS and those with DS reached an early maximum developmental level due to cognitive constraints.     

Lexico-semantic processing in Williams syndrome

People with Williams syndrome, a neurodevelopmental genetic syndrome, typically have good language skills as compared to other cognitive abilities, as far as intellectual disability is concerned. They have a large vocabulary and they frequently use uncommon or rarely-used words. This has led some authors to consider that they have a peculiar semantic system, different from that of people with typical development. In this study, we tested this hypothesis by comparing the performance of a group of young adults with Williams syndrome to a control group using various lexico-semantic tasks, including semantic and phonological fluency. The results indicate that the semantic system of people with Williams syndrome does not seem to differ much from those in the control group because the words they produced were similar to those of the control group with regard to word frequency, length or the typicality of the responses within the categories.     

Nature and nurture: Williams syndrome across cultures

This study is concerned with ways in which children with Williams syndrome (WS), a rare neurodevelopmental disorder arising from a hemizygous deletion in chromosome band 7q11.23 including the gene for elastin (ELN) and approximately 20 surrounding genes, are affected by social mores of vastly differing cultures: the United States and Japan. WS presents a compelling model for the investigation because its genetic phenotype is well defined and results in an uneven cognitive profile as well as a social phenotype typical of the syndrome including overt over-friendliness toward strangers. While a number of research groups have been studying the cognitive strengths and weaknesses of individuals with WS in various countries, there have not been studies to date that explore the social phenotype in WS across different cultures. This study examines the ways in which social behavior in WS, stemming from specific genetic underpinnings, might be mediated by cultural expectations. We conducted a cross-cultural study using an instrument that measures aspects of sociability commonly found among people with WS. Quantitative analyses revealed a significant effect of diagnostic category in that in both countries, children with WS were rated as significantly higher in global sociability and more likely to approach strangers than were their normal counterparts. There was also an effect of culture, in that regardless of category, WS and normal children in Japan were rated lower than their counterparts in the US. We suggest that the excessively social phenotype of children with Williams syndrome, although markedly present across cultures, appears to vary in its intensity by culture. This is an intriguing illustration of interactions between nature and nurture.     

A componential view of theory of mind: evidence from Williams syndrome

In this paper we argue that there are two distinct components of a theory of mind: a social-cognitive and a social-perceptual component. Evidence for this proposal is presented from various sources, including studies of children with Williams syndrome, a rare genetic neurodevelopmental disorder. Earlier work has demonstrated that people with Williams syndrome appear to be spared in the social-perceptual component of a theory of mind. In this paper we present evidence that they are not spared in the social-cognitive component of theory of mind. Three experiments with young children with Williams syndrome were conducted. In each experiment the children with Williams syndrome were compared to age-, IQ-, and language-matched children with Prader-Willi syndrome, and children with non-specific mental retardation. The experiments used different measures of theory of mind ability, including false belief (Experiment 1), explanation of action (Experiment 2), and recognition of emotional expressions (Experiment 3). In none of these experiments did the children with Williams syndrome evidence superior performance compared to the control groups. The results from this and other studies on Williams syndrome support the view that the social-cognitive and social-perceptual components of a theory of mind are dissociable. In Williams syndrome only the latter components, which are linked to distinct neurobiological substrates, are spared.     

Face-to-face interference in typical and atypical development

Visual communication cues facilitate interpersonal communication. It is important that we look at faces to retrieve and subsequently process such cues. It is also important that we sometimes look away from faces as they increase cognitive load that may interfere with online processing. Indeed, when typically developing individuals hold face gaze it interferes with task completion. In this novel study we quantify face interference for the first time in Williams syndrome (WS) and Autism Spectrum Disorder (ASD). These disorders of development impact on cognition and social attention, but how do faces interfere with cognitive processing? Individuals developing typically as well as those with ASD (n = 19) and WS (n = 16) were recorded during a question and answer session that involved mathematics questions. In phase 1 gaze behaviour was not manipulated, but in phase 2 participants were required to maintain eye contact with the experimenter at all times. Looking at faces decreased task accuracy for individuals who were developing typically. Critically, the same pattern was seen in WS and ASD, whereby task performance decreased when participants were required to hold face gaze. The results show that looking at faces interferes with task performance in all groups. This finding requires the caveat that individuals with WS and ASD found it harder than individuals who were developing typically to maintain eye contact throughout the interaction. Individuals with ASD struggled to hold eye contact at all points of the interaction while those with WS found it especially difficult when thinking.     

Atypical development of language and social communication in toddlers with Williams syndrome

Williams syndrome (WS) is a genetic disorder which results in an uneven cognitive profile. Despite superior language compared to other syndromes in the phenotypic outcome, toddlers with WS are as delayed in their language onset and early linguistic development as are toddlers with other syndromes. The cause of this delay in WS is as yet unknown. In a series of experiments, we examined whether atypical socio‐interactive precursors to language could contribute to the explanation of the late language onset and atypical developmental pathways observed in WS. Experiment 1 showed that despite superficially good social skills, toddlers with WS were only proficient at dyadic interaction. They were impaired in triadic interaction, essential for the referential uses of language, and showed none of the correlations between socio‐interactive markers and language seen in the typical controls. Experiment 2 focused on the comprehension and production of referential pointing. Again, the WS group was impaired, despite vocabulary levels higher than those of typically developing controls. Finally, Experiment 3 examined fine motor skills. The WS lack of pointing could not be explained in terms of motor impairments, since the WS toddlers were proficient at fine motor control, such as the pincer grip. Overall, our data indicate that the early stages of WS language follow an atypical pathway. The findings challenge the frequent claims in the literature that individuals with Williams syndrome have preserved linguistic and social skills.     

Psychopathology and behavior problems in children and adolescents with Williams syndrome: Distinctive relationships with cognition

Several studies have documented the high prevalence of psychopathology and behavior problems in Williams syndrome (WS). However, the links between cognitive development and such symptoms need further clarification. Our study aims to expand current knowledge on levels of behavior problems and its links to cognition in a sample of Brazilian individuals with WS. A total of 25 children and adolescents with WS and their parents participated in this study. The participants’ IQs were assessed with the Wechsler Scales of Intelligence (for children or adults) and parental reports of psychopathology/behavior problems were collected using the Child Behavior Checklist (CBCL). The presence of clinically significant attention problems was a main feature in our sample of children and adolescents with WS. In the children, higher IQ scores were found to be significantly associated with less externalizing problems, while in the adolescents cognitive abilities were found to be associated with less internalizing symptoms. These results provide further insight into the links between psychopathology and behavior problems and cognitive abilities in WS, and suggest the need to take age into consideration when analyzing such relationships.     

Intact perception of biological motion in the face of profound spatial deficits: Williams syndrome

Williams syndrome (WS) is a rare genetic disorder that results in profound spatial cognitive deficits. We examined whether individuals with WS have intact perception of biological motion, which requires global spatial integration of local motion signals into a unitary percept of a human form. Children with WS, normal mental-age-matched children, and normal adults viewed point-light-walker (PLW) displays portraying a human figure walking to the left or right. Children with WS were as good as or better than control children in their ability to judge the walker's direction, even when it was masked with dynamic noise that mimicked the local motion of the PLW lights. These results show that mechanisms underlying the perception of at least some kinds of biological motion are unimpaired in children with WS. They provide the first evidence of selective sparing of a specialized spatial system in individuals with a known genetic impairment.     

Environmental sound recognition by timbre in children with Williams syndrome

Anecdotal reports have described children with Williams syndrome (WS) as presenting outstanding skills for recognizing environmental sounds by their timbre. This has led to suggest that the skills for environmental sound recognition by timbre are highly developed in WS. Furthermore, the term hypertimbria has been proposed to refer to this feature. However, no academic research has assessed these skills in WS. This study therefore aimed to contrast the reports on the highly developed skills for environmental sound recognition by timbre in children with WS. An environmental sound recognition task was administered to children with WS, children with Down syndrome of the same chronological age and cognitive level, and chronological age-matched typically developing children. Participants with WS performed significantly lower than their typically developing peers and no significant differences were found between the WS and Down syndrome groups. Unlike previous reports, this study points out that in WS environmental sound recognition by timbre does not constitute a phenotypic strength either in absolute or relative terms. Results suggest that children with WS do not present hypertimbria or preserved skills for timbre recognition. We discuss the implications of these results for theories of cognitive modularity.     

Brain imaging in neurogenetic conditions: realizing the potential of behavioral neurogenetics research

Behavioral neurogenetics research is a new method of scientific inquiry that focuses on investigation of neurodevelopmental dysfunction associated with specific genetic conditions. This research method provides a powerful tool for scientific inquiry into human gene-brain-behavior linkages that complements more traditional research approaches. In particular, the use of specific genetic conditions as models of common behavioral and cognitive disorders occurring in the general population can reveal insights into neurodevelopmental pathways that might otherwise be obscured or diluted when investigating more heterogeneous, behaviorally defined subject groups. In this paper, we review five genetic conditions that commonly give rise to identifiable neurodevelopmental and neuropsychiatric disability in children: fragile X syndrome, velo-cardio-facial syndrome, Williams syndrome, Turner syndrome, and Klinefelter syndrome. While emphasis is placed on describing the brain morphology associated with these conditions as revealed by neuroimaging studies, we also include information pertaining to molecular genetic, postmortem, and neurobehavioral investigations to illustrate how behavioral neurogenetics research can contribute to an improved understanding of brain disorders in childhood.     

Before and after the vocabulary spurt: two modes of word acquisition?

This paper focuses on early lexical development, and especially the period around 18 months known as the vocabulary spurt. We first propose that this period corresponds to a shift from an associationist to a referential lexical acquisition mechanism following the developmental coupling of specific pre‐linguistic and cognitive abilities. This latter mechanism would allow the acquisition of genuine words, i.e. links between phonetically specified sound patterns and object categories. We then review the literature on early lexical acquisition by typically developing infants and infants with Down and Williams syndrome, and report some data that were recently collected on this issue. We conclude that the data so far are congruent with our proposal, but because they remain insufficient, we propose some future research that focuses on the relation between pre‐linguistic and cognitive developments.     

People with Williams syndrome process faces holistically

This study compared the performance of 47 adolescents and adults with Williams syndrome to 39 age-matched controls on a face recognition task. Using the whole-part paradigm developed by Tanaka and his colleagues, we found that although performance overall was lower in the participants with Williams syndrome, both groups showed similar patterns of performance across the different conditions. Both groups performed significantly better in the whole-face than in the isolated-part test condition for upright faces, but not for inverted faces. The whole-face advantage only in the upright condition provides strong evidence that people with Williams syndrome encode and recognize faces holistically in the same way as normal controls, suggesting the use of similar underlying neurocognitive mechanisms. These findings contradict earlier reports in the literature that people with Williams syndrome process faces abnormally.