Williams Syndrome Children Research Articles

Characteristics of early cognitive development in children with Williams syndrome: a prospective cohort study

To investigate the early cognitive development characteristics of children with Williams syndrome (WS) at different age stages. From September 2018 to June 2023, 106 children diagnosed with WS at the Department of Pediatric Health Care, Children's Hospital, Zhejiang University School of Medicine, aged 1 to <5 years, were prospectively enrolled. All children underwent Gesell developmental diagnostic assessments to analyze the cognitive development characteristics of WS children across different age groups. The average age of the 106 WS children was (3.1±1.2) years; 58 were male, and 48 were female. There were no significant differences in developmental levels between males and females in the five domains of gross motor skills, fine motor skills, language, personal-social skills, and adaptive behavior (P>0.05). The incidence rates of mild, moderate, severe, and profound developmental disabilities among children of different age groups showed no significant differences (P>0.05). Comparisons of developmental levels in gross motor skills, language, personal-social skills, and adaptive behavior among different age groups were also not statistically significant (P>0.05). With the increase of age, the developmental level of fine motor skills showed a decreasing trend (P<0.05). There were no significant differences in verbal IQ and non-verbal IQ within each age group of WS children (P>0.05). The overall developmental level of WS children stabilizes with age, and their early language abilities do not significantly exceed their non-verbal abilities.

Longitudinal profiles of late phonological development in children with Williams syndrome

Williams syndrome (WS) is a genetic neurodevelopmental disorder characterized by language skills above what is expected considering non-verbal intelligence. Research on phonological development is scarce, with many studies focusing on grammar in children and adolescents. In one of our previous studies transversally explored the profiles of late phonological development in Spanish-speaking WS children, adolescents, and adults, while our objective is to longitudinally determine these profiles for WS children based on present error indexes in spontaneous speech. Participants were seven WS children (aged 3;7–8;2), engaging in two spontaneous conversations within a 6-month interval. They were compared cross-sectionally with 240 typically developing (TD) children aged 3–6 years, divided into six groups. All speech samples were transcribed and analyzed with the CLAN software package of the CHILDES Project. Phonological profiles were established on the basis of phonological error indexes obtained dividing absolute frequency of errors by the total number of words produced. WS children showed a mean reduction of more than 25% in the absolute frequency of phonological errors after 6 months. As for the comparison with the normative groups, their error index was consistent with the stage of expansion in TD, however, after 6 months, this was consistent with the stage of stabilization. This atypical acceleration in phonological development could be related to lexical growth in the context of relative preservation of phonological memory. Furthermore, the trajectories of late phonological development in WS children might not be linear, as postulated by neuroconstructivist models, suggesting the need for intervention approaches specifically adapted to the phonological profiles of WS children.

The place and role of the civil sector in the inclusive education and development of children with Williams syndrome (also) through music

Williams syndrome (WS) is an extremely rare genetic disorder. Approximately 1 in every 20 000 people has WS. Because of this, most people have never even met a child with WS. WS occupies a unique place among genetic disorders because of the fact that, in addition to a unique mix of difficulties, symptoms and abnormalities, some of their abilities and performance in certain intellectual areas are adequate or average, and in many cases above average. Relatively high level of ability includes good communication skills, outstanding verbal skills, sociability and good musical abilities with highly sensitive hearing, good musical pitch and musicality, and a very positive attitude towards music. As is typically the case for rare disorders, the most important pillar of their advocacy is the civil sphere, where NGOs and foundations support WS children and families. The great affinity and positive relationship with music justifies that a prominent part of development and inclusion are specifically music-related activities, music therapy activities. The main objective of our research is to map NGOs in Europe and beyond whose activities focus on WS patients and their families. The basis for mapping the organizations is to summarize their aims, activities and achievements and to highlight their music-related activities in line with the mission of inclusion. Our main objective is to show that the development and rehabilitation of WS patients through music and musical activities is a significant and integral part of their care within the organized framework and possibilities of the civil sector.

Evaluating the challenges and needs of parents caring for children with Williams syndrome: A preliminary study from Poland

BackgroundAlthough physical, cognitive and behavioural manifestations of Williams syndrome (WS) affect every dimension of caregivers lives, no studies on the parental experiences of caring for a WS child have to date been carried out in Poland. MethodsIn order to identify the challenges and needs of Polish carers of WS children a survey was conducted with 32 family caregivers who were supported by the Polish Williams Syndrome Association. ResultsWhile caregivers were mostly challenged by their WS child’s behaviours, health problems and mood swings, many parents experienced fatigue, intimacy problems with the partner and deterioration of mental health. They were also burdened by the lack of time for themselves and work restrictions resulting from caregiving responsibilities. Even though parents positively assessed quality of medical care for WS children, still many expressed their dissatisfaction both with the way the healthcare system for WS children works in Poland and complained about the doctors’ lack of knowledge about WS, access to specialist care and lack of support from government and social institutions. Although many parents stressed positive impact of rising WS child, more than half experienced role captivity or role overload and felt not being understood by others. They also experienced variety of distressing emotions, including impatience, emotional lability, helplessness, anxiety and depression. ConclusionsAlthough many WS parents stressed the affirmative aspect of raising WS child this research shows that the burden of caring for such a child goes far beyond clinical aspects and seriously affects every aspect of parents’ lives, including their mental health, daily lives, family, their professional and social lives. Because apart from the daily challenges related to caring for a WS child, parents’ dealings with the healthcare system and support services represent major problems there is a the need for a bio-psychosocial approach to WS that should include not only WS children, but also their caregivers. What this paper adds?1. It analyses the challenges and needs of parents caring for children with Williams syndrome;2. It provides evidence that the impact of caring for WS children goes far beyond clinical aspects and seriously affects every aspect of parents’ lives, including their mental health, daily lives, family, their professional and social lives;3. It also shows that, apart from the daily challenges related to caring for a WS child, parents’ dealings with the healthcare system and support services represent major problems.4. Thereby, it highlights the importance of incorporating a bio-psychosocial approach to WS that should include not only WS children, but also their caregivers.

Internalising and Externalising Symptoms and Their Association with the Family Environment in Young Children with Williams Syndrome: A Longitudinal Study.

Williams Syndrome (WS) involves high rates of psychopathology across the lifespan. However, little is known about the early, longitudinal trajectory of internalising/externalising symptoms or the association between these and the family environment in WS. WS (n = 16; aged 2 years, 2 months to 9 years, 5 months) and typically developing or TD (n = 46; aged 2 years, 2 months to 11 years, 1 month) children were assessed on two occasions over 2.5 years utilising parent report questionnaires-the Child Behaviour Checklist and the Family Environment Scale. No statistically significant changes were found in CBCL/psychopathology profiles across timepoints, on average, for either WS or TD children. However, reliable change scores showed WS children had considerable variability in CBCL scores over time. Cross-sectionally, the WS group showed higher scores (reflecting more psychopathology) compared to TD controls at both time points across most CBCL subscales, with elevated overall psychopathology problems identified in 56-68% of WS children (versus 8% in TD controls). Psychopathology was not associated with sex, chronological age, or cognitive ability in WS. Conflict in the family environment was positively associated with higher Attention Problems at Time 1 in the WS group, whilst the TD group showed associations between family conflict and total psychopathology problems at both time points and between family cohesion and total psychopathology problems at Time 2. Family environment did not differ between groups, except for lower engagement in intellectual and cultural activities in WS. Findings highlight variable Internalising and Externalising Problems in young WS children over time, with greater biological than environmental contributions to psychopathology in WS.

Extracorporeal membrane oxygenation outcomes in children with Williams syndrome: a review of the ELSO registry.

Williams syndrome (WS) results from a microdeletion that usually involves the elastin gene, leading to generalized arteriopathy. Cardiovascular anomalies are seen in 80% of WS patients, including supravalvular aortic stenosis (SVAS), pulmonary artery stenosis (PAS), and pulmonary stenosis (PS). Sudden death associated with procedural sedation and in the perioperative period in WS children have been reported. This study aims to describe extracorporeal membrane oxygenation (ECMO) use in WS children, identify risk factors for hospital mortality of WS patients, and compare outcomes between WS children and non-WS children with SVAS, PAS, and PS. Children 0-18 years-old in the Extracorporeal Life Support Organization (ELSO) Registry with a primary or secondary diagnosis of WS, SVAS, PAS, or PAS were included. Included were 50 WS children and 1222 non-WS children with similar cardiac diagnoses. ECMO use increased over time in both groups (p = 0.93), with most cases occurring in the current era. WS children were younger (p = 0.004), weighed less (p = 0.048), had a pulmonary indication for ECMO (50% vs 10%, p < 0.001), and were placed more on high frequency ventilation (p < 0.001) than non-WS patients. Despite reporting a respiratory indication, most (84%) WS patients were placed on VA-ECMO. There were no significant differences between the two groups in terms of pre-ECMO cardiac arrest, ECMO duration, or reason for ECMO discontinuation. Both groups had a mortality rate of 48% (p = 1.00). No risk factors for WS mortality were identified.

Gait characteristics of children with Williams syndrome with impaired visuospatial recognition: a three-dimensional gait analysis study.

Williams syndrome (WS) is a genetically based neurodevelopmental disorder characterized by intellectual disability and impaired visuospatial recognition. The aim of this study was to analyze the gait characteristics of WS children with impaired visuospatial recognition using a three-dimensional gait analysis (3DGA) to clarify the gait adaptation needed to compensate for it. 3DGA was performed in 8 WS children with impaired visuospatial recognition (mean age, 11.8years) and 9 age-, sex-, height-, and weight-matched controls. Clinical data, fundamental motor tests, and gait variables while walking on a flat surface and walking up a mat were compared between the two groups, and the correlations between variables were analyzed in the WS children. WS children showed impairment of balance function without muscle weakness. In walking on a flat surface, the WS group showed reduced walking speed, short step length, increased variability of step length, increased knee flexion throughout the stance phase, increased horizontal pelvic range of motion (ROM), and a low Gait Deviation Index and a high Gait Profile Score, which are indices of gait quality. In walking up a mat, the WS group showed further reduced walking speed and decreased sagittal hip flexion and ankle dorsiflexion ROM in the swing phase. Impaired balance function was significantly correlated with increased variability of step length and decreased sagittal ankle dorsiflexion ROM in the swing phase. The detailed gait pattern of WS children with impaired visuospatial recognition was presented. These findings show that impaired visuospatial recognition and balance function contribute to gait adaptation.

Physical growth and development characteristics of children with Williams syndrome aged 0-24 months in Zhejiang Province.

Background The objective of this study was to evaluate the physical growth and development characteristics of children with Williams syndrome (WS) aged 0-24 months, and provide help for early diagnosis of WS. Methods A total of 32 cases of children (17 males and 15 females) aged 0-24 months who were diagnosed with WS were enrolled between 2008 and 2017. These children were divided into four different groups: 1-6 months (six cases), 7-12 months (eight cases), 12-18 months (nine cases) and 19-24 months (nine cases). Meanwhile, a total of 32 healthy children (17 males and 15 females) were enrolled in the study from the Department of Health Care for physical examination in our hospital as the control group and matched with each divided group. Weight and height were measured, and meanwhile birth weight and height were also asked and recorded. Results There was no statistically significant difference in birth height between the two groups (p>0.05), and birth weight and the height and weight of the children with WS in the four groups were significantly lower than those of the children in the normal control (NC) group (p>0.05). When the corresponding age of WS children was compared to the Nine City Growth Curve Standards in China, 97% of cases were lagging behind in physical growth and development. Conclusions WS children often have the features of early slow physical growth, which provides certain help for the early diagnosis of WS. Therefore, for younger children, facial features combined with an accurate and objective physical growth assessment and ultrasonic cardiogram can greatly improve the screening rate.

Biomechanical Description of Phonation in Children Affected by Williams Syndrome

The voice of persons with Williams syndrome (WS) is described as hoarse with a deep and unstable fundamental frequency (f0). These observations may be justified by the deficit of elastin due to a haplo-insufficiency in the ELN gene characteristic of the syndrome. In view of the possible relationship between elastin deficit and dysphonia, a study of the dynamic function of WS phonation was conducted by means of biomechanical analysis. In order to assess the presence of dysphonic symptoms and their degree of severity, the biomechanical description of WS phonation has been evaluated in terms of dynamic mass and viscoelasticity estimates. Glottal biomechanical features such as vocal fold dynamic mass, stiffness, unbalances, and laryngeal tremor of 12 children with WS aged 3 to 8 years (five girls and seven boys) have been estimated and compared with the normative phonation of 97 children with typical development (53 girls and 44 boys). The results show that WS children show differences in f0, vocal fold mass and stiffness, phonation stability, glottal contact defects, and laryngeal tremor. The conclusions may help to make a more complete view of the connection between WS and dysphonia based on objective assessments.

Dissociation of spatial memory systems in Williams syndrome.

Williams syndrome (WS), a genetic deletion syndrome, is characterized by severe visuospatial deficits affecting performance on both tabletop spatial tasks and on tasks which assess orientation and navigation. Nevertheless, previous studies of WS spatial capacities have ignored the fact that two different spatial memory systems are believed to contribute parallel spatial representations supporting navigation. The place learning system depends on the hippocampal formation and creates flexible relational representations of the environment, also known as cognitive maps. The spatial response learning system depends on the striatum and creates fixed stimulus-response representations, also known as habits. Indeed, no study assessing WS spatial competence has used tasks which selectively target these two spatial memory systems. Here, we report that individuals with WS exhibit a dissociation in their spatial abilities subserved by these two memory systems. As compared to typically developing (TD) children in the same mental age range, place learning performance was impaired in individuals with WS. In contrast, their spatial response learning performance was facilitated. Our findings in individuals with WS and TD children suggest that place learning and response learning interact competitively to control the behavioral strategies normally used to support human spatial navigation. Our findings further suggest that the neural pathways supporting place learning may be affected by the genetic deletion that characterizes WS, whereas those supporting response learning may be relatively preserved. The dissociation observed between these two spatial memory systems provides a coherent theoretical framework to characterize the spatial abilities of individuals with WS, and may lead to the development of new learning strategies based on their facilitated response learning abilities.

Thinking inside the box: Spatial frames of reference for drawing in Williams syndrome and typical development

BackgroundSuccessfully completing a drawing relies on the ability to accurately impose and manipulate spatial frames of reference for the object that is being drawn and for the drawing space. Typically developing (TD) children use cues such as the page boundary as a frame of reference to guide the orientation of drawn lines. Individuals with Williams syndrome (WS) typically produce incohesive drawings; this is proposed to reflect a local processing bias. AimsAcross two studies, we provide the first investigation of the effect of using a frame of reference when drawing simple lines and shapes in WS and TD groups (matched for non-verbal ability). Methods and proceduresIndividuals with WS (N=17 Experiment 1; N=18 Experiment 2) and TD children matched by non-verbal ability drew single lines (Experiment One) and whole shapes (Experiment Two) within a neutral, incongruent or congruent frame. The angular deviation of the drawn line/shape, relative to the model line/shape, was measured. Outcomes and resultsBoth groups were sensitive to spatial frames of reference when drawing single lines and whole shapes, imposed by a frame around the drawing space. Conclusions and implicationsA local processing bias in WS cannot explain poor drawing performance in WS.

Mother-Child Interaction as a Window to a Unique Social Phenotype in 22q11.2 Deletion Syndrome and in Williams Syndrome.

Mother-child interactions in 22q11.2 Deletion syndrome (22q11.2DS) and Williams syndrome (WS) were coded for maternal sensitivity/intrusiveness, child's expression of affect, levels of engagement, and dyadic reciprocity. WS children were found to express more positive emotions towards their mothers compared to 22q11.2DS children and those with developmental delay in a conflict interaction. During the same interaction, dyads of 22q11.2DS children were characterized by higher levels of maternal intrusiveness, lower levels of child's engagement and reduced reciprocity compared to dyads of typically developing children. Finally, 22q11.2DS children with the COMT Met allele showed less adaptive behaviors than children with the Val allele. Dyadic behaviors partially coincided with the distinct social phenotypes in these syndromes and are potential behavioral markers of psychopathological trajectory.

Abnormalities in Pattern of Lateralization in Relation to Visuospatial Short Term Memory in Children with Williams Syndrome

Williams syndrome (WS) is a genetic disorder characterised by significant intellectual disability. Initial studies indicate that children with WS have a profound bias for information in the top left of visual arrays. Study 1, using a visuospatial memory test for items presented in a3×3matrix, found a significant top left bias in WS children relative to controls. Study 2 used a probe-based memory test with arrays in which items appeared with equal probability in each position. Relative to controls, WS children showed a significant top and left bias. In Study 3, the same children engaged in a visual search task and again, a top and left bias was found in the WS group. It is concluded that children with WS display atypical laterality, which might be explained by abnormal saccadic movements, by abnormalities involving development of the dorsal stream or by uneven cortical development.

Sleep problems and language development in toddlers with Williams syndrome

Sleep and related maternal beliefs were assessed in a narrow age range of 18 children with Williams syndrome (WS) and 18 typically developing (TD) children. WS is a rare genetic disorder characterised by a complex physical, cognitive and behavioural phenotype. High prevalence of sleep difficulties in older children and adults with WS have been reported. Parents completed 6 questionnaires: the Brief Infant Sleep Questionnaire, Infant Sleep Vignettes Interpretation Scale, Pittsburgh Sleep Quality Index of Parents, Child Behaviour Checklist, MacArthur Communicative Development Inventory for Infants - Words and Gestures, and the Major (ICD-10) Depression Inventory. Compared to TD children, those with WS had shorter night sleep, more night wakings and wakefulness according to parental report. Regression analyses revealed that a proportion of the variance in language development scores in WS children could be explained by night sleep duration. Compared to control parents, the mothers of the WS group were more likely to describe their child's sleep as problematic and had higher rates of involvement with child sleep, yet they had a lesser tendency to interpret sleep problems as signs of distress and a greater tendency to emphasise limit setting. Approximately half of both groups of mothers experienced poor sleep quality. This was also related to maternal mood, and night wakefulness in the children with WS. This is the first study to quantify sleep difficulties in young children with WS in a narrow age range using maternal report. The possible negative effects on maternal sleep and mood, and the link between night sleep and language development in young children with WS, requires further detailed investigation.

Why Do Only Some Institutionalized Children Become Indiscriminately Friendly? Insights From the Study of Williams Syndrome

Why do some institutionalized children develop indiscriminate behavior (IB) while others do not? Considering children with Williams syndrome (WS) may provide an answer because IB has been observed routinely among individuals with this rare genetic neurodevelopmental disorder. By conceiving WS as a natural genetic model that mimics the indiscriminate phenotype and, more importantly, is associated with the deletion of genes in a specific region, we propose an integrative conceptual framework that underscores the dynamic developmental interplay between genes, endophenotypes, and environment. In this article, we consider the etiology of IB among institutionalized children, which emphasizes environmental factors, followed by the effect of such behavior on WS children's hypersociability, which highlights the crosstalk between genes and neuropsychological features in programming their distinctive social-emotional and behavioral phenotype. We propose new hypotheses regarding the etiopathogeny of IBs in institutionalized children, particularly the prediction of specific Gene × Environment interactions.

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.

Phenotypic psychiatric characterization of children with Williams syndrome and response of those with ADHD to methylphenidate treatment

Williams syndrome (WS) is associated with cognitive deficits, special behavioral phenotype, and high rates of psychiatric disorders. The aims of the present study were: (1) To compare the rates of psychiatric disorders and repetitive behaviors in children with WS to children with idiopathic developmental disability (DDs); (2) To longitudinally assess the change in psychiatric disorders during adolescence in WS; (3) To assess retrospectively the effectiveness and safety of methylphenidate (MPH) treatment in WS children with ADHD. The study consisted of a cohort of 38 children and adolescents (age 13.1 ± 5.2 years) with WS and a sample of age-matched DDs (age 15.0 ± 3.1 years). A current follow-up evaluation was conducted after 5.6 ± 1.6 years for 25 subjects (65.8%) of the WS cohort. The rate of most psychiatric disorders was found similar in children with WS and DD controls. Specific phobia, especially from noises, obsessive-compulsive symptoms (e.g., aggressive obsessions and repetitive questions), and stereotypic behaviors (e.g., glancing), were more common in WS than DDs. In a longitudinal follow-up of the WS children, we found a decrease in the rate of anxiety disorders. In addition, a clinically significant improvement was reported in 72.2% of WS children with ADHD following MPH treatment. Sadness/unhappiness was the most common side effect associated with MPH treatment in WS, occurring in 2/3 of treated individuals. The present study further elucidates the neuropsychiatric phenotype of WS. Our results also suggest that MPH treatment for ADHD in WS warrants future prospective controlled trials.

Williams syndrome: a relationship between genetics, brain morphology and behaviour

Genetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ∼28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual deficiencies (i.e. low-moderate intelligence quotient, visuospatial deficits) yet relatively preserving what is uniquely human (i.e. language and social-emotional cognition). Therefore, WS provides a privileged setting for investigating the relationship between genes, brain and the consequent complex human behaviour. We used in vivo anatomical magnetic resonance imaging analysing cortical surface-based morphometry, (i.e. surface area, cortical volume, cortical thickness, gyrification index) and cortical complexity, which is of particular relevance to the WS genotype-phenotype relationship in 22 children (2.27-14.6 years) to compare whole hemisphere and lobar surface-based morphometry between WS (n = 10) and gender/age matched normal controls healthy controls (n = 12). Compared to healthy controls, WS children had a (1) relatively preserved Cth; (2) significantly reduced SA and CV; (3) significantly increased GI mostly in the parietal lobe; and (4) decreased CC specifically in the frontal and parietal lobes. Our findings are then discussed with reference to the Rakic radial-unit hypothesis of cortical development, arguing that WS gene deletions may spare Cth yet affecting the number of founder cells/columns/radial units, hence decreasing the SA and CV. In essence, cortical brain structure in WS may be shaped by gene-dosage abnormalities.

Contour integration deficit in Williams Syndrome children

Contour integration deficit in Williams Syndrome children

Strangers and Spiders: How Young Children with Williams Syndrome Respond to Social and Non-social Fear-eliciting Events

Strangers and Spiders: How Young Children with Williams Syndrome Respond to Social and Non-social Fear-eliciting Events