The proceedings of the 15th professional conference on Williams Syndrome.

Williams Syndrome (WS) is a contiguous gene deletion disorder, caused by the deletion of approximately 26-28 genes from chromosome 7 (7q11.23). Individuals with WS have complex medical, developmental, and behavioral features, requiring multidisciplinary and interdisciplinary collaboration. Guidelines detailing the identification, evaluation, and monitoring of individuals with WS need clarification, especially for primary care providers who are first-line in their management. This report summarizes the proceedings of the 2016 Professional Conference on WS in Columbus, OH. Presentations were directed towards primary care providers and subspecialists, emphasizing evidence-based practices for treating the prevalent medical and behavioral features of WS. Included in this report are findings from a panel of cardiovascular experts discussing three case studies on treatment of hypertension and the use of sedation or anesthesia for non-cardiac procedures. Abstracts from individual expert presenters are included, covering various medical and behavioral topics, and providing updates in management of WS individuals. The following topics were discussed: differences in phenotypes of 7q11.23 deletion versus duplication, growth parameters, endocrine concerns, sleep difficulties, behaviors to monitor, and pharmacological options, the neurodevelopmental profile of WS individuals, and the importance of monitoring medical and behavioral concerns as WS individuals transition to adulthood.

Contrast-marking prosodic emphasis in Williams syndrome: results of detailed phonetic analysis.

BACKGROUND: Past reports on the speech production of individuals with Williams syndrome (WS) suggest that their prosody is anomalous and may lead to challenges in spoken communication. While existing prosodic assessments confirm that individuals with WS fail to use prosodic emphasis to express contrast, those reports typically lack detailed phonetic analysis of speech data. The present study examines the acoustic properties of speech prosody, aiming for the future development of targeted speech interventions. AIMS: The study examines the three primary acoustic correlates of prosodic emphasis (duration, intensity, F0) and determines whether individuals with WS have difficulty in producing all or a particular set of the three prosodic cues. METHODS & PROCEDURES: Speech produced by 12 individuals with WS and 12 chronological age (CA)-matched typically developing individuals were recorded. A sequential picture-naming task elicited production of target phrases in three contexts: (1) no contrast: gorilla with a racket → rabbit with a balloon; (2) contrast on the animal: fox with a balloon → rabbit with a balloon; and (3) contrast on the object: rabbit with a ball → rabbit with a balloon. The three acoustic correlates of prosodic prominence (duration, intensity and F0) were compared across the three referential contexts. OUTCOMES & RESULTS: The two groups exhibited striking similarities in their use of word duration and intensity for expressing contrast. Both groups showed the reduction and enhancement of final lengthening, and the enhancement and reduction of intensity difference for the animal contrast and for the object contrast conditions, respectively. The two groups differed in their use of F0: the CA group produced higher F0 for the animal than for the object regardless of the context, and this difference was enhanced when the animal noun was contrastive. In contrast, the WS group produced higher F0 for the object than for the animal when the object was contrastive. CONCLUSIONS & IMPLICATIONS: The present data contradict previous assessment results that report a lack of prosodic skills to mark contrast in individuals with WS. The methodological differences that may account for this variability are discussed. The present data suggest that individuals with WS produce appropriate prosodic cues to express contrast, although their use of pitch may be somewhat atypical. Additional data and future speech comprehension studies will determine whether pitch modulation can be targeted for speech intervention in individuals with WS.

Handedness and corpus callosal morphology in Williams syndrome.

Williams syndrome is a neurodevelopmental genetic disorder caused by a hemizygous deletion on chromosome 7q11.23, resulting in atypical brain structure and function, including abnormal morphology of the corpus callosum. An influence of handedness on the size of the corpus callosum has been observed in studies of typical individuals, but handedness has not been taken into account in studies of callosal morphology in Williams syndrome. We hypothesized that callosal area is smaller and the size of the splenium and isthmus is reduced in individuals with Williams syndrome compared to healthy controls, and examined age, sex, and handedness effects on corpus callosal area. Structural magnetic resonance imaging scans were obtained on 25 individuals with Williams syndrome (18 right-handed, 7 left-handed) and 25 matched controls. We found that callosal thickness was significantly reduced in the splenium of Williams syndrome individuals compared to controls. We also found novel evidence that the callosal area was smaller in left-handed participants with Williams syndrome than their right-handed counterparts, with opposite findings observed in the control group. This novel finding may be associated with LIM-kinase hemizygosity, a characteristic of Williams syndrome. The findings may have significant clinical implications in future explorations of the Williams syndrome cognitive phenotype.

Learning without representational change: development of numerical estimation in individuals with Williams syndrome.

Experience engenders learning, but not all learning involves representational change. In this paper, we provide a dramatic case study of the distinction between learning and representational change. Specifically, we examined long- and short-term changes in representations of numeric magnitudes by asking individuals with Williams syndrome (WS) and typically developing (TD) children to estimate the position of numbers on a number line. As with TD children, accuracy of WS children's numerical estimates improved with age (Experiment 1) and feedback (Experiment 2). Both long- and short-term changes in estimates of WS individuals, however, followed an atypical developmental trajectory: as TD children gained in age and experience, increases in accuracy were accompanied by a logarithmic-to-linear shift in estimates of numerical magnitudes, whereas in WS individuals, accuracy increased but logarithmic estimation patterns persisted well into adulthood and after extensive training. These findings suggest that development of numerical estimation in WS is both arrested and atypical.

Brief Report: Evaluating the Effectiveness of Music to Obtain More Accurate Blood Pressure Readings in Children with Williams Syndrome.

This study examined if listening to music will improve the accuracy of blood pressure (BP) readings in children with Williams syndrome (WS). Fifty-two participants (7-12 years) were randomly assigned to a music or non-music group. BPs were obtained at two time points. There was a significant decrease in both systolic and diastolic BP from Time 1 to Time 2 for everyone. Participants from the music group had lower systolic BP readings at Time 2 than participants in the non-music group (Cohen's d = 0.33). Systolic BP readings were approximately 3.8 mmHg lower in the music group. Music may be beneficial in obtaining more accurate systolic BP readings in children with WS.

Research Review: Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype.

This review critically examines the research findings which characterize the cognitive, behavioral, and neuroanatomical features of Williams syndrome (WS). This article analyzes 178 published studies in the WS literature covering the following areas: 1) General intelligence, 2) Language skills, 3) Visuospatial and face processing skills, 4) Behavior patterns and hypersociability, 5) Musical abilities, and 6) Brain structure and function. We identify methodological issues relating to small sample size, use and type of control groups, and multiple measures of task performance. Previously described 'peaks' within the cognitive profile are closely examined to assess their veracity. This review highlights the need for methodologically sound studies that utilize multiple comparison groups, developmental trajectories, and longitudinal analyses to examine the WS phenotype, as well as those that link brain structure and function to the cognitive and behavioral phenotype of WS individuals.

Williams Syndrome and Music: A Systematic Integrative Review.

Background: Researchers and clinicians have often cited a strong relationship between individuals with Williams syndrome (WS) and music. This review systematically identified, analyzed, and synthesized research findings related to WS and music. Methods: Thirty-one articles were identified that examined this relationship and were divided into seven areas. This process covered a diverse array of methodologies, with aims to: (1) report current findings; (2) assess methodological quality; and (3) discuss the potential implications and considerations for the clinical use of music with this population. Results: Results indicate that individuals with WS demonstrate a high degree of variability in skill and engagement in music, presenting with musical skills that are more in line with their cognitive abilities than chronological age (CA). Musical strengths for this population appear to be based more in musicality and expressivity than formal musical skills, which are expressed through a heightened interest in music, a greater propensity toward musical activities, and a heightened emotional responsiveness to music. Individuals with WS seem to conserve the overall structure of musical phrases better than they can discriminate or reproduce them exactly. The affinity for music often found in this population may be rooted in atypical auditory processing, autonomic irregularities, and differential neurobiology. Conclusions: More studies are needed to explore how this affinity for music can be harnessed in clinical and educational interventions.

Use and Effectiveness of Sleep Medications by Parent Report in Individuals with Williams Syndrome.

OBJECTIVE: Sleep disorders are common in individuals with Williams syndrome (WS), and sleep disturbance has a significant negative effect on attention, learning, and behavior. The use of sleep-inducing medicine in individuals with WS has not been widely investigated. The objective of this study was to evaluate the use and effectiveness of sleep medications among a large sample of individuals with WS by parent survey. METHODS: A survey of the use and effectiveness of sleep medications was completed by 513 (of 2846) members of the Williams Syndrome Association. The online survey asked for the age at initiation, degree of effectiveness (helpful, somewhat helpful, and not helpful), and side effects. RESULTS: One hundred thirty participants (25%) indicated that their family member with WS had taken medication to help with sleep. Melatonin was the most commonly reported medication taken for sleep, with 91% of parents reporting that it was "helpful" or "somewhat helpful" for their child with WS. Those who reported taking melatonin reported very few, if any, side effects. CONCLUSION: This parent-completed survey is a preliminary study showing the positive benefit of melatonin for individuals with WS who have disrupted sleep. The findings support the need for further study of the use of melatonin, in addition to behavioral sleep aids, given evidence that sleep disturbance negatively influences cognition and behavior.

Adaptive Behavior and Development of Infants and Toddlers with Williams Syndrome.

Williams syndrome (WS) is a neurodevelopmental disorder that causes deficits in adaptive behavior, difficulties eating and sleeping, cognitive delays, and delayed development. Although researchers have conducted characterizations of children and adults with WS, less is known about young children with this disorder. This study characterizes the developmental and adaptive behavior features of 16 infants and toddlers with WS aged 3 months - 5 years. Data for this project was obtained from 2007 to 2014, and includes parent report data and standardized developmental testing. Thirty-one percent (31.3%) of parents reported that their infant/toddler with WS had sleeping problems and 58.3% reported feeding difficulties. Levels of adaptive behavior were in the Mildly Delayed range as measured by the Adaptive Behavior Assessment System, Second Edition. Self-care skills such as feeding or dressing oneself were significantly weaker than skills needed to function in the community, such as recognizing his/her home or throwing away trash. The difficulty with self-care skills is hypothesized to be related to the reported difficulties with eating and sleeping. Motor skills were significantly lower than both cognitive and language skills on the Bayley Scales of Infant and Toddler Development, Third Edition. The current study highlights the need for early intervention in these young children across all areas of development, particularly in self-care skills.

Music lessons are associated with increased verbal memory in individuals with Williams syndrome.

Williams syndrome (WS) is a genetic disorder characterized by intellectual delay and an affinity for music. It has been previously shown that familiar music can enhance verbal memory in individuals with WS who have had music training. There is also evidence that unfamiliar, or novel, music may also improve cognitive recall. This study was designed to examine if a novel melody could also enhance verbal memory in individuals with WS, and to more fully characterize music training in this population. We presented spoken or sung sentences that described an animal and its group name to 44 individuals with WS, and then tested their immediate and delayed memory using both recall and multiple choice formats. Those with formal music training (average duration of training 4½ years) scored significantly higher on both the spoken and sung recall items, as well as on the spoken multiple choice items, than those with no music training. Music therapy, music enjoyment, age, and Verbal IQ did not impact performance on the memory tasks. These findings provide further evidence that formal music lessons may impact the neurological pathways associated with verbal memory in individuals with WS, consistent with findings in typically developing individuals.

Pragmatic language assessment in Williams syndrome: a comparison of the Test of Pragmatic Language-2 and the Children's Communication Checklist-2.

PURPOSE: Individuals with Williams syndrome (WS) are recognized as having a strong desire for social relationships, yet many of them have difficulty forming and maintaining peer relationships. One cause may be impairments in pragmatic language. The current study compared the assessment of pragmatic language skills in individuals with WS using the Test of Pragmatic Language-Second Edition (TOPL-2; Phelps-Terasaki & Phelps-Gunn, 2007) and the Children's Communication Checklist-Second Edition (CCC-2; Bishop, 2003). METHOD: Twenty children and adolescents diagnosed with WS were given the TOPL-2, and their parents completed the CCC-2. RESULTS: The TOPL-2 identified 8 of the 14 older children (ages 8-16 years) as having pragmatic language impairment and all of the 6 younger children (ages 6-7 years) as having such. In comparison, the CCC-2 identified 6 of the 14 older children and 2 of the 6 younger children as having pragmatic language impairment. The older group also had a higher composite score than the younger group on the CCC-2. CONCLUSION: The TOPL-2 identified significantly more participants as having pragmatic language impairment than did the CCC-2. The TOPL-2 may be more useful in assessing pragmatic language in older children than younger children. The results offer important preliminary clinical implications of language measures that may be beneficial in the assessment of individuals with WS.

Caregiver survey of pharmacotherapy to treat attention deficit/hyperactivity disorder in individuals with Williams syndrome.

Williams syndrome (WS) is a genetic condition characterized by a unique neurocognitive and behavioral profile, including increased incidence of attention deficit/hyperactivity disorder (ADHD). The purpose of the present study was to examine the perceived helpfulness and side effects of medications used to treat ADHD (methylphenidate class, amphetamine class, atomoxetine) in individuals with WS. This was accomplished with a survey of parents/caregivers of individuals with WS through the Williams Syndrome Association. Five-hundred twelve (512) parents/caregivers responded to the survey regarding their child's/adult child's use of ADHD medications. Twenty-seven percent (27%) of the individuals had been prescribed a medication for ADHD, most commonly a methylphenidate class medication. OROS-methylphenidate was reported as the most helpful methylphenidate class formulation, with 74% reporting it at least somewhat helpful. Survey participants reported similar side effects as typically developing controls, but to a greater degree. Irritability was the most commonly endorsed side effect of an ADHD medication (38%). Individuals reported use of stimulant medications in the presence and absence of underlying cardiac conditions, with 56% of ADHD medication users reporting supravalvular aortic stenosis, 36% pulmonary artery stenosis, and 25% systemic hypertension. Individuals taking ADHD medications were more likely to report dental problems (p=0.004). Additional studies are needed to further investigate these findings and examine short-versus long-acting stimulant medications and dosage effects.

Continuous cognitive dynamics of the evaluation of trustworthiness in williams syndrome.

The decision to approach or avoid an unfamiliar person is based in part on one's evaluation of facial expressions. Individuals with Williams syndrome (WS) are characterized in part by an excessive desire to approach people, but they display deficits in identifying facial emotional expressions. Likert-scale ratings are generally used to examine approachability ratings in WS, but these measures only capture an individual's final approach/avoid decision. The present study expands on previous research by utilizing mouse-tracking methodology to visually display the nature of approachability decisions via the motor movement of a computer mouse. We recorded mouse movement trajectories while participants chose to approach or avoid computer-generated faces that varied in terms of trustworthiness. We recruited 30 individuals with WS and 30 chronological age-matched controls (mean age = 20 years). Each participant performed 80 trials (20 trials each of four face types: mildly and extremely trustworthy; mildly and extremely untrustworthy). We found that individuals with WS were significantly more likely than controls to choose to approach untrustworthy faces. In addition, WS participants considered approaching untrustworthy faces significantly more than controls, as evidenced by their larger maximum deviation, before eventually choosing to avoid the face. Both the WS and control participants were able to discriminate between mild and extreme degrees of trustworthiness and were more likely to make correct approachability decisions as they grew older. These findings increase our understanding of the cognitive processing that underlies approachability decisions in individuals with WS.

Parent report of antidepressant, anxiolytic, and antipsychotic medication use in individuals with Williams syndrome: effectiveness and adverse effects.

Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage regarding their child or adult with WS. Twenty-four percent (24%) of the individuals had been prescribed an SSRI medication, while 12% had been prescribed another type of antidepressant or anxiolytic. Overall, 81% of respondents indicated that SSRI medications were either "Helpful" or "Somewhat Helpful", with paroxetine reported to be the least helpful. Sixty-four percent (64%) of survey participants reported that non-SSRI antidepressants and anxiolytics were either "Helpful" or "Somewhat Helpful" in treating symptoms of anxiety. Side effects for the antidepressants and anxiolytics were typically neurological in nature. Ten percent (10%) of the survey participants reported taking an antipsychotic medication, with risperidone and quetiapine described as more helpful than aripiprazole. Medication effectiveness may be related to the impact on serotonin levels. These findings call for further studies of medication usage in WS in order to improve their quality of life.

Effect of musical experience on verbal memory in Williams syndrome: evidence from a novel word learning task.

Williams syndrome (WS) is a neurogenetic developmental disorder characterized by an increased affinity for music, deficits in verbal memory, and atypical brain development. Music has been shown to improve verbal memory in typical individuals as well as those with learning difficulties, but no studies have examined this relationship in WS. The aim of our two studies was to examine whether music can enhance verbal memory in individuals with WS. In Study 1, we presented a memory task of eight spoken or sung sentences that described an animal and identified its group name to 38 individuals with WS. Study 2, involving another group of individuals with WS (n=38), included six spoken or sung sentences that identified an animal group name. In both studies, those who had participated in formal music lessons scored significantly better on the verbal memory task when the sentences were sung than when they were spoken. Those who had not taken formal lessons showed no such benefit. We also found that increased enjoyment of music and heightened emotional reactions to music did not impact performance on the memory task. These compelling findings provide the first evidence that musical experience may enhance verbal memory in individuals with WS and shed more light on the complex relationship between aspects of cognition and altered neurodevelopment in this unique disorder.

Auditory cortical volumes and musical ability in Williams syndrome.

Individuals with Williams syndrome (WS) have been shown to have atypical morphology in the auditory cortex, an area associated with aspects of musicality. Some individuals with WS have demonstrated specific musical abilities, despite intellectual delays. Primary auditory cortex and planum temporale volumes were manually segmented in 25 individuals with WS and 25 control participants, and the participants also underwent testing of musical abilities. Left and right planum temporale volumes were significantly larger in the participants with WS than in controls, with no significant difference noted between groups in planum temporale asymmetry or primary auditory cortical volumes. Left planum temporale volume was significantly increased in a subgroup of the participants with WS who demonstrated specific musical strengths, as compared to the remaining WS participants, and was highly correlated with scores on a musical task. These findings suggest that differences in musical ability within WS may be in part associated with variability in the left auditory cortical region, providing further evidence of cognitive and neuroanatomical heterogeneity within this syndrome.

Approachability and the amygdala: insights from Williams syndrome.

Williams syndrome (WS) is a genetic neurodevelopmental disorder in which hypersociability is a characteristic feature. Given that the amygdala has been identified as an integral component of the neural system underlying sociability, researchers have suggested that the abnormal amygdala volumes found in individuals with WS may play a role in their hypersociability. The aim of this study was to examine the relationship between amygdala volume and hypersociability, as measured by approachability ratings, in 22 individuals with WS and 22 normal controls matched on chronological age, sex, and handedness. We confirmed previous findings of increased amygdala volumes and higher approachability ratings of both 'positive' and 'negative' faces in individuals with WS. A positive relationship between right amygdala volume and approachability ratings was found in individuals with WS, particularly ratings of 'negative' faces. The results unexpectedly revealed that individuals with WS report using features other than the eyes and mouth to determine approachability, particularly when they are younger. These findings support the theory that amygdala dysfunction in WS is related to their hypersociability. Furthermore, we propose that individuals with WS use atypical cognitive strategies compared to controls to determine approachability.

Organ transplantation, organ donation and mental retardation.

We reviewed the literature on accessibility and outcomes of organ transplantation in individuals with mental retardation (MR) and on the prevalence of organ donation in this population. Six centers have published outcome data on renal transplantation in 34 individuals with MR. The one- and three-yr patient survival rates were 100% and 90%, respectively. The studies reported good compliance with post-transplant medications due to consistent support from family members or caregivers. The outcome studies for liver and heart transplantation among these individuals are limited. The literature on organ donation in individuals with MR is mostly concerned with legal issues. The courts generally permit organ donations when such is in the best interests of the donor.

Trasplante de órganos, donación de órganos y discapacidad mental / No disponible

Hemos revisado la literatura sobre la accesibilidad y resultado del trasplante de órganos en la personas con discapacidad intelectual (DI) y sobre la prevalencia de la donación de órganos en esta población. Seis centros han publicado datos con resultados sobre el trasplante renal en 34 personas con discapacidad intelectual (muchas de ellas con síndrome de Down). Las tasas de supervivencia al año y a los 3 años fueron del 100% y del 90%, respectivamente. Los estudios mostraron un buen cumplimiento del régimen de medicación post-transplante, debido al permanente apoyo por parte de los miembros de la familia o de los cuidadores. Los estudios sobre resultados en el trasplante de hígado o de corazón son más limitados. La literatura sobre donación de órganos por parte de estas personas se centra más en los aspectos legales. Los tribunales permiten en general la donación de órganos cuando ello resulta en beneficio del donante (AU)

No disponible