Williams Syndrome Research Articles

Human Genetics of Semilunar Valve and Aortic Arch Anomalies.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.

Idiopathic infantile hypercalcemia with a <i>CYP24A1 </i>variant triggered by vitamin D supplementation in fortified milk: a case report

Idiopathic infantile hypercalcemia with a <i>CYP24A1 </i>variant triggered by vitamin D supplementation in fortified milk: a case report

Neuronal Gtf2i deletion alters mitochondrial and autophagic properties

Gtf2i encodes the general transcription factor II-I (TFII-I), with peak expression during pre-natal and early post-natal brain development stages. Because these stages are critical for proper brain development, we studied at the single-cell level the consequences of Gtf2i’s deletion from excitatory neurons, specifically on mitochondria. Here we show that Gtf2i’s deletion resulted in abnormal morphology, disrupted mRNA related to mitochondrial fission and fusion, and altered autophagy/mitophagy protein expression. These changes align with elevated reactive oxygen species levels, illuminating Gtf2i’s importance in neurons mitochondrial function. Similar mitochondrial issues were demonstrated by Gtf2i heterozygous model, mirroring the human condition in Williams syndrome (WS), and by hemizygous neuronal Gtf2i deletion model, indicating Gtf2i’s dosage-sensitive role in mitochondrial regulation. Clinically relevant, we observed altered transcript levels related to mitochondria, hypoxia, and autophagy in frontal cortex tissue from WS individuals. Our study reveals mitochondrial and autophagy-related deficits shedding light on WS and other Gtf2i-related disorders.

Level of Negative Emotional States among Parents of Speech and Language Delay

Background: The prevalence and impact of delayed speech and language disorders in children have increasingly become a concern, particularly regarding the psychological well-being of their parents. Prior research has explored various factors influencing parental stress in families with children suffering from different developmental disorders, including Down, Williams, Fragile X, and Prader-Willi syndromes. However, there is a need to understand specifically how delayed speech and language disorders in children affect the emotional states of their parents. Objective: This study aimed to evaluate the levels of stress, anxiety, and depression among parents of children with primary and secondary speech and language delays. It sought to identify the predominant emotional states in these parents and understand the relationship between the child's developmental status and the parent's emotional well-being. Methods: A cross-sectional study was conducted in Multan, involving parents of 70 children with delayed speech and language disorders. Using the Depression Anxiety Stress Scales (DASS) Inventory, parents were assessed for levels of stress, anxiety, and depression. The study employed a non-probability convenient sampling technique, and the data were analyzed using the Statistical Package for the Social Sciences (SPSS), Version 23. Results: The analysis showed significant correlations between depression, anxiety, and stress. Depression had a mean score of 6.986, anxiety had a mean score of 5.529, and stress showed the highest mean score at 7.971. These results indicate that stress is the most prevalent emotional issue among these parents, exceeding the levels of depression and anxiety. Conclusion: The study concludes that parents of children with delayed speech and language disorders in Multan experience high levels of stress, overshadowing other negative emotional states like depression and anxiety. These findings highlight the need for targeted support and interventions for these families, focusing not only on the child's development but also on the mental health and well-being of the caregivers.

Transposons in the Williams-Beuren Syndrome Critical Region are Associated with Social Behavior in Assistance Dogs.

A strong signature of selection in the domestic dog genome is found in a five-megabase region of chromosome six in which four structural variants derived from transposons have previously been associated with human-oriented social behavior, such as attentional bias to social stimuli and social interest in strangers. To explore these genetic associations in more phenotypic detail-as well as their role in training success in a specialized assistance dog program-we genotyped 1001 assistance dogs from Canine Companions for Independence®, including both successful graduates and dogs released from the training program for behaviors incompatible with their working role. We collected phenotypes on each dog using puppy-raiser questionnaires, trainer questionnaires, and both cognitive and behavioral tests. Using Bayesian mixed models, we found strong associations (95% credibility intervals excluding zero) between genotypes and certain behavioral measures, including separation-related problems, aggression when challenged or corrected, and reactivity to other dogs. Furthermore, we found moderate differences in the genotypes of dogs who graduated versus those who did not; insertions in GTF2I showed the strongest association with training success (β = 0.23, CI95% = -0.04, 0.49), translating to an odds-ratio of 1.25 for one insertion. Our results provide insight into the role of each of these four transposons in canine sociability and may inform breeding and training practices for working dog organizations. Furthermore, the observed importance of the gene GTF2I supports the emerging consensus that variation in GTF2I genotypes and expression have important consequences for social behavior broadly.

Early Communicative Development in Williams Syndrome: A Longitudinal Case Study.

Individuals with Williams Syndrome (WS) have a specific and atypical neuropsychological profile, where language is above what is expected for their mental age, although it shows a late onset. There exists only one longitudinal study in infants younger than 20 months old with WS about early language precursors (joint attention, referential and instrumental behaviors, pointing gesture, verbal tags). The aim of this investigation is to evaluate these precursors in a baby with WS (8 to 18 months). Seven sessions of systematic observation were performed (six at baby's home, one at the Early Childhood Assistance center). The Battelle Developmental Inventory was used to evaluate the baby's development in two occasions (12 and 18 months). The results show an atypical development, and he is 5-6 months under what is expected for his chronological age. Attention towards objects prevails over preference for faces, but this one tends to increase. The pointing gesture does not emerge at the end of the observation period and therefore follows the first words that appear. The implications for the comprehension of the early linguistic profile in WS are discussed, as well as the implications for specific intervention strategies in the context of early childhood care.

GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders.

Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome featuring hypersociability, while duplication causes 7q11.23 microduplication syndrome (7Dup), frequently exhibiting autism spectrum disorder (ASD). Converging evidence indicates GTF2I as key mediator of the cognitive-behavioral phenotypes, yet its role in cortical development and behavioral hallmarks remains largely unknown. We integrated proteomic and transcriptomic profiling of patient-derived cortical organoids, including longitudinally at single-cell resolution, to dissect 7q11.23 dosage-dependent and GTF2I-specific disease mechanisms. We observed dosage-dependent impaired dynamics of neural progenitor proliferation, transcriptional imbalances, and highly specific alterations in neuronal output, leading to precocious excitatory neuron production in 7Dup, which was rescued by restoring physiological GTF2I levels. Transgenic mice with Gtf2i duplication recapitulated progenitor proliferation and neuronal differentiation defects alongside ASD-like behaviors. Consistently, inhibition of lysine demethylase 1 (LSD1), a GTF2I effector, was sufficient to rescue ASD-like phenotypes in transgenic mice, establishing GTF2I-LSD1 axis as a molecular pathway amenable to therapeutic intervention in ASD.

Optical coherence tomography angiography findings in Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a rare genetic disease characterized by psychomotor delay, cardiovascular, musculoskeletal, and endocrine problems. Retinal involvement, which is not well characterized, has also been described. The purpose of this cross-sectional study is to describe the characteristics in optical coherence tomography (OCT) and OCT-angiography (OCTA) of patients with WBS. We included patients with WBS confirmed by genetic analysis. The patients underwent OCT (30° × 25°, 61 B-scans) and OCTA (10° × 10° and 20° × 20°) examinations, all centered on the. Data on retinal thickness (total, inner and outer layers) and foveal morphology on OCT and vessel and perfusion density in OCTA (VD and PD, respectively) were collected. These data were compared with an age-matched control group. 22 eyes of 22 patients with WBS (10 females, mean age 31.5 years) were included. Retinal thickness (and specifically inner retinal layers) in OCT was significantly reduced in all sectors (central, parafoveal, and perifoveal) compared to the control group (p < 0.001 in all sectors). Fovea in WBS eyes was broader and shallower than controls. The PD and VD in both 10 and 20 degrees of fields in OCTA was significantly reduced in patients with WBS, in all vascular plexa (all p < 0.001). This study is the first to quantify and demonstrate retinal structural and microvascular alterations in patients with WBS. Further studies with longitudinal data will reveal the potential clinical relevance of these alterations.

Oral language interventions can improve language outcomes in children with neurodevelopmental disorders: A systematic review and meta-analysis.

Young people who fail to develop language as expected face significant challenges in all aspects of life. Unfortunately, language disorders are common, either as a distinct condition (e.g., Developmental Language Disorder) or as a part of another neurodevelopmental condition (e.g., autism). Finding ways to attenuate language problems through intervention has the potential to yield great benefits not only for the individual but also for society as a whole. This meta-analytic review examined the effect of oral language interventions for children with neurodevelopmental disorders. The last electronic search was conducted in April 2022. Intervention studies had to target language skills for children from 2 to 18 years of age with Developmental Language Disorder, autism, intellectual disability, Down syndrome, Fragile X syndrome, and Williams syndrome in randomised controlled trials or quasi-experimental designs. Control groups had to include business-as-usual, waiting list, passive or active conditions. However, we excluded studies in which the active control group received a different type, delivery, or dosage of another language intervention. Eligible interventions implemented explicit and structured activities (i.e., explicit instruction of vocabulary, narrative structure or grammatical rules) and/or implicit and broad activities (i.e., shared book reading, general language stimulation). The intervention studies had to assess language skills in receptive and/or expressive modalities. The search provided 8195 records after deduplication. Records were screened by title and abstract, leading to full-text examinations of 448 records. We performed Correlated and Hierarchical Effects models and ran a retrospective power analysis via simulation. Publication bias was assessed via p-curve and precision-effect estimate. We examined 38 studies, with 46 group comparisons and 108 effects comparing pre-/post-tests and eight studies, with 12 group comparisons and 21 effects at follow-up. The results showed a mean effect size of d = 0.27 at the post-test and d = 0.18 at follow-up. However, there was evidence of publication bias and overestimation of the mean effects. Effects from the meta-analysis were significantly related to these elements: (1) receptive vocabulary and omnibus receptive measures showed smaller effect sizes relative to expressive vocabulary, grammar, expressive and receptive discourse, and omnibus expressive tests; and (2) the length of the intervention, where longer sessions conducted over a longer period of time were more beneficial than brief sessions and short-term interventions. Neither moderators concerning participants' characteristics (children's diagnosis, diagnostic status, age, sex, and non-verbal cognitive ability and severity of language impairment), nor those regarding of the treatment components and implementation of the language interventions (intervention content, setting, delivery agent, session structure of the intervention or total number of sessions) reached significance. The same occurred to indicators of study quality. The risk of bias assessment showed that reporting quality for the studies examined in the review was poor. In sum, the current evidence base is promising but inconclusive. Pre-registration and replication of more robust and adequately powered trials, which include a wider range of diagnostic conditions, together with more long-term follow-up comparisons, are needed to drive evidence-based practice and policy.

Melatonin in Neurodevelopmental Disorders: A Critical Literature Review.

The article presents a review of the relationships between melatonin and neurodevelopmental disorders. First, the antioxidant properties of melatonin and its physiological effects are considered to understand better the role of melatonin in typical and atypical neurodevelopment. Then, several neurodevelopmental disorders occurring during infancy, such as autism spectrum disorder or neurogenetic disorders associated with autism (including Smith-Magenis syndrome, Angelman syndrome, Rett's syndrome, Tuberous sclerosis, or Williams-Beuren syndrome) and neurodevelopmental disorders occurring later in adulthood like bipolar disorder and schizophrenia, are discussed with regard to impaired melatonin production and circadian rhythms, in particular, sleep-wake rhythms. This article addresses the issue of overlapping symptoms that are commonly observed within these different mental conditions and debates the role of abnormal melatonin production and altered circadian rhythms in the pathophysiology and behavioral expression of these neurodevelopmental disorders.

Development of emotion comprehension in children with autism spectrum disorder and Williams syndrome.

Although research has shed light on the development of emotion comprehension in typically developing children, little is known about emotion comprehension in children who are developing atypically. Thus, this study examined the developmental trajectory of emotion understanding in non-clinical (NC) children and children with autism spectrum disorder (ASD) and Williams syndrome (WS) using a Test of Emotion Comprehension. In the test, we measured children's understanding of (I) recognition of emotions based on facial expressions, (II) external causes of emotions, (III) desire-based emotions, (IV) belief-based emotions, (V) the influence of a reminder on a present emotional state, (VI) regulating an experienced emotion, (VII) hiding an emotional state, (VIII) mixed emotions, and (IX) moral emotions. A Bayesian modeling approach was applied to compare the developmental trajectories of emotion understanding across the syndrome groups. The results revealed that NC children and children with WS followed significantly different developmental trajectories in specific aspects of emotion understanding, while children with ASD followed a very similar path to NC children. Children with ASD and NC children gradually developed an understanding of each component of emotion comprehension as they matured. However, the understanding of some components, such as desire-based emotions, hiding an emotional state, and moral emotions, in children with WS was affected by their Autism Spectrum Quotient scores. This is one of the first cross-syndrome studies to assess the development of emotion comprehension in children with ASD and WS, providing important insights for understanding the nature of disability and advancing the development of intervention programs.

Electrocardiograms Do Not Detect Myocardial Ischemia in Patients With Williams Syndrome and Nonsyndromic Elastin Arteriopathy With Coronary Artery Stenosis

Coronary artery stenosis (CAS) may affect up to 27% of patients with Williams syndrome (WS), which may lead to myocardial ischemia. Patients with WS face a 25- to 100-fold greater risk of sudden cardiac death, frequently linked to anesthesia. Assessing CAS requires either imaging while under general anesthesia or intraoperative assessment, with the latter considered the gold standard. Our study aimed to identify electrocardiogram (ECG) markers of myocardial ischemia in patients with WS or nonsyndromic elastin arteriopathy and documented CAS. We retrospectively reviewed patients with WS/elastin arteriopathy who underwent supravalvar aortic stenosis surgery and CAS assessment from January 1, 2006 to April 30, 2021. A pediatric electrophysiologist, not aware of the patients' CAS status, reviewed their preoperative ECGs for markers of ischemia. We assessed associations of study parameters using Wilcoxon rank-sum and Fisher's exact tests. Of 34 patients, 62% were male, with a median age of 20 months (interquartile range: 8 to 34). CAS was present in 62% (21 of 34), 76% of whom (16 of 21) were male. There were no ECG indicators of myocardial ischemia in patients with CAS. In conclusion, CAS was present in >1/2 the children with WS/elastin arteriopathy who underwent repair of supravalvar aortic stenosis. CAS in WS/nonsyndromic elastin arteriopathy does not appear to exhibit typical ECG-detectable myocardial ischemia. ECGs are not a useful screening tool for CAS in WS/elastin arteriopathy. Given the high anesthesia-related cardiac arrest risk, other noninvasive indicators of CAS are needed.

Abstract 17825: Heart Rate Fragmentation Analysis May Suggest Non-Autonomic Markers of Sudden Cardiac Death Risk in Adults With Williams-Beuren Syndrome

Background: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by a chromosomal microdeletion (7q11.23). It confers increased arrhythmia and sudden cardiac death (SCD) risk. Mechanisms underlying this risk remain obscure. We recently found HRV abnormalities in individuals with WBS that are known to correlate with sudden death risk in diabetes and following MI and stroke. Heart rate fragmentation (HRF) correlated with adverse CV events in some studies where HRV failed to identify high-risk subjects. Some argue that HRF quantifies non-autonomic CV modulators. We, therefore, sought to further explore non-autonomic modulators of cardiovascular disease by performing HRF analysis in a cohort of adults with WBS. Hypothesis: We hypothesize that those with WBS may exhibit increased sudden death risk from mechanisms not detected by conventional HRV measures. Aims: We aim to 1) Identify biomarkers that are predictive of SCD risk in WBS, and 2) Determine if HRF quantifies non-autonomic CV modulators. Methods: We performed HRF analyses on 24hr ECGs in subjects with WBS (n=18) and age- and sex-matched controls (n=18) enrolled in a prospective NIH study. HRF analyses include the percentage of inflection points (PIP), percentages of hard (PIP H ) and soft (PIP S ) inflection points, and the distribution of “words”, where W 0 ,W 1 ,W 2 , W 3 represent sequences of 4 beats with 0, 1, 2, or 3 inflection points. Inflection points were defined as a change in NN by more than 1/s, where ‘s’ is the sampling frequency. Mann-Whitney tests were used to compare HRF in subjects vs. controls. Spearman’s correlation was used to compare HRF to traditional HRV. Results: HRF markers (PIP, PIP S , and W 3 ) were significantly elevated in WBS subjects (P&lt;0.003)(Fig 1A-C). PIP S and W 3 were negatively correlated with parasympathetic markers HF power and SD1 among WBS subjects (Fig 1D). Conclusion: HRF may quantify some non-autonomic modulators of sudden death risk in those with WBS.

Abstract 18657: Diagnostic Yield of Whole Genome Sequencing in Congenital Heart Disease: Data From the UK 100,000 Genomes Project

Congenital heart disease (CHD) is the most common birth defect affecting around 1% global live births. The aetiology of CHD is poorly understood: while a number genetic loci have already been identified, the majority of cases remain unexplained. Many CHD cases occur with additional abnormalities, or as part of a defined syndrome (eg. Noonan or CHARGE syndromes). The 100,000 Genomes Project conducted whole genome sequencing for patients with a range of rare diseases and cancers in partnership with the UK National Health Service. We analysed clinical and genetic data from the project in 2638 participants with CHD, including both primary CHD cases and secondary cases who have CHD as part of a syndromic presentation but were recruited under other disease categories. Both cohorts are primarily composed of patients with CHD accompanied by additional extra-cardiac abnormalities without a prior diagnosis of a defined syndrome. We found that families recruited as primary CHD cases were significantly less likely to have been classed as “solved cases” (indicating a pathogenic variant has been identified) than phenotypically similar secondary CHD cases (5.4% primary, 16.2% secondary; p = 6.78х -11 ). This is primarily due to differences in the gene lists used in analysis, with the majority of diagnoses in both groups due to genes not included in the CHD gene panel (83% primary and 97% secondary cases). Expanding standard CHD screening to include a wider range of syndromic CHD genes is likely to increase the diagnostic yield for the primary CHD cohort by more than two-fold. Copy number variants (CNVs) also contribute to CHD, especially in cases with additional abnormalities. CHD cases have a significantly higher burden of both deletions (p = 1.00х10 -5 ) and duplications (p = 0.009) than an ethnically-matched control cohort. However, only 7 of 2638 participants have CNVs in known CHD-causative regions such as the 22q11.2 or Williams-Beuren syndrome regions indicating novel CNVs are likely to contribute to a significant number of cases. Wider screening of syndromic CHD genes and novel copy number variants is likely significantly increase the diagnostic yield for CHD both within the 100,000 Genomes Project and in healthcare settings, and potentially yield novel CHD-associated loci.

Williams–Beuren syndrome shapes the gut microbiota metaproteome

Williams–Beuren syndrome (WBS) is a rare genetic neurodevelopmental disorder with multi-systemic manifestations. The evidence that most subjects with WBS face gastrointestinal (GI) comorbidities, have prompted us to carry out a metaproteomic investigation of their gut microbiota (GM) profile compared to age-matched healthy subjects (CTRLs). Metaproteomic analysis was carried out on fecal samples collected from 41 individuals with WBS, and compared with samples from 45 CTRLs. Stool were extracted for high yield in bacterial protein group (PG) content, trypsin-digested and analysed by nanoLiquid Chromatography-Mass Spectrometry. Label free quantification, taxonomic assignment by the lowest common ancestor (LCA) algorithm and functional annotations by COG and KEGG databases were performed. Data were statistically interpreted by multivariate and univariate analyses. A WBS GM functional dissimilarity respect to CTRLs, regardless age distribution, was reported. The alterations in function of WBSs GM was primarily based on bacterial pathways linked to carbohydrate transport and metabolism and energy production. Influence of diet, obesity, and GI symptoms was assessed, highlighting changes in GM biochemical patterns, according to WBS subsets’ stratification. The LCA-derived ecology unveiled WBS-related functionally active bacterial signatures: Bacteroidetes related to over-expressed PGs, and Firmicutes, specifically the specie Faecalibacterium prausnitzii, linked to under-expressed PGs, suggesting a depletion of beneficial bacteria. These new evidences on WBS gut dysbiosis may offer novel targets for tailored interventions.

Evaluating Procedural Performance: A Composite Outcome for Aortic and Pulmonary Valvuloplasty in Congenital Cardiac Catheterization.

Safety events and technical success (TS) have been previously reported for aortic and pulmonary valvuloplasty, but a composite performance measure as a novel, patient-centered strategy has neither been developed nor been studied. This study aims to refine a procedural performance (PP) variable, a composite of TS and procedural safety, for isolated, standard-risk aortic and pulmonary valvuloplasty. A multicenter review was performed using data from the Congenital Cardiac Catheterization Project on Outcomes registry. Data were collected for all cases of isolated balloon aortic and pulmonary valvuloplasty from 2014 through 2017. Patients were excluded if they were aged <1 month, were inpatient at the time of the procedure, or had significant comorbidities, such as Williams or Noonan syndrome. Criteria for TS were developed and categorized (optimal, satisfactory, and unsatisfactory) by expert consensus based on previous outcome research. Adverse events (AE) were categorized by severity (level 1-5) using established criteria. Level 4 and 5 severity AE were considered high-severity AE. Using criteria of TS and AE severity, PP was divided into 3 composite outcome classes. Factors correlating with class III (suboptimal) PP were analyzed. There were 169 cases of aortic and 270 cases of pulmonary valvuloplasty in the cohorts. In the aortic valvuloplasty cohort, a suboptimal PP (class III) occurred in 14% of cases, mostly due to high-severity AE (7%). No significant correlation between patient or case characteristics and PP was demonstrated. In the pulmonary valvuloplasty cohort, class III PP occurred in 9% of cases, predominantly due to residual valve gradient, which correlated with lower weight (P = .02). We designed a composite variable of PP consisting of TS and safety as a comprehensive measure of outcome. Incorporating both TS and AE may better reflect patient outcome than each metric measured separately. PP indices may identify areas for further investigation and quality improvement.

Williams–Beuren Syndrome in Adulthood for Hernia Repair: Anesthetic Challenges and Tutorial on Atrial Fibrillation

Williams–Beuren Syndrome in Adulthood for Hernia Repair: Anesthetic Challenges and Tutorial on Atrial Fibrillation

Developmental characteristics of Williams-Beuren syndrome and evaluation of adaptive behavioral skills.

Williams-Beuren syndrome (WBS) is a rare genetic disorder with delays in language and cognitive development, but, with increased awareness of clinical features and a reliable diagnostic test, WBS is becoming more widely recognized in childhood. Adaptive behavior skills and/or maladaptive behavior are important for the prognosis of individuals with WBS. The aim of this study was to investigate the clinical and developmental characteristics of patients with WBS and further increase awareness about it by evaluating the adaptive skills and maladaptive behaviors of the patients. The data of WBS patients followed-up at the Developmental Behavioral Pediatrics Unit were reviewed. Patient data on perinatal and postnatal history, developmental stages, physical and neurological examination findings were collected. The International Guide for Monitoring Child Development (GMCD) was administered to each child. In addition, semistructured interviews were conducted with the parents using the Vineland Adaptive Behavior Scales, Second edition (Vineland-II). A total of 12 patients diagnosed with WBS via detection of the 7q11.23 deletion, of whom 6 were girls, were retrospectively reviewed. The mean age at the time of review was 54.6 ± 32.5 months. The mean age at first presentation to the Developmental Behavioral Pediatrics Outpatient Clinic was 15 ± 11.5 months. In the first developmental evaluation using the GMCD, there was a delay in fine and gross motor domains in 6 patients, in the language domains in 4 patients, and in all of the domains in 2 patients. Findings with Vineland-II showed socialization and communication domains as strengths, but the daily living skills and motor skills domains were weaknesses. In terms of maladaptive behavior, the patients tended to frequently have behavioral problems, neurodevelopmental disease, anxiety disorders, eating problems, and sleeping problems. This retrospective review of 12 patients indicated a general delay in overall development, and confirmed impairment in both adaptive and maladaptive functioning in WBS.

No transfer of arousal from other’s eyes in Williams syndrome

Typically developing humans automatically synchronize their arousal levels, resulting in pupillary contagion, or spontaneous adaptation of pupil size to that of others. This phenomenon emerges in infancy and is believed to facilitate social interaction. Williams syndrome (WS) is a genetic condition characterized by a hyper-social personality and social interaction challenges. Pupillary contagion was examined in individuals with WS (n = 44), age-parallel-matched typically developing children and adults (n = 65), and infants (n = 79). Bayesian statistics were used. As a group, people with WS did not show pupillary contagion (Bayes factors supporting the null: 25–50) whereas control groups did. This suggests a very early emerging atypical developmental trajectory. In WS, higher pupillary contagion was associated with lower autistic symptoms of social communication. Diminished synchronization of arousal may explain why individuals with WS have social challenges, whereas synchronization of arousal is not a necessary correlate of high social motivation.

Intensive Care Unit Analgosedation After Cardiac Surgery in Children with Williams Syndrome : a Matched Case-Control Study.

Cardiovascular abnormalities are common in patients with Williams syndrome and frequently require surgical intervention necessitating analgesia and sedation in a population with a unique neuropsychiatric profile, potentially increasing the risk of adverse cardiac events during the perioperative period. Despite this risk, the overall postoperative analgosedative requirements in patients with WS in the cardiac intensive care unit have not yet been investigated. Our primary aim was to examine the analgosedative requirement in patients with WS after cardiac surgery compared to a control group. Our secondary aim was to compare the frequency of major ACE and mortality between the two groups. Matched case-control study. Pediatric CICU at a Tertiary Children's Hospital. Patients with WS and age-matched controls who underwent cardiac surgery and were admitted to the CICU after cardiac surgery between July 2014 and January 2021. None. Postoperative outcomes and total doses of analgosedative medications were collected in the first six days after surgery for the study groups. Median age was 29.8 (12.4-70.8) months for WS and 23.5 (11.2-42.3) months for controls. Across all study intervals (48h and first 6 postoperative days), there were no differences between groups in total doses of morphine equivalents (5.0mg/kg vs 5.6mg/kg, p = 0.7 and 8.2mg/kg vs 10.0mg/kg, p = 0.7), midazolam equivalents (1.8mg/kg vs 1.5mg/kg, p = 0.4 and 3.4mg/kg vs 3.8mg/kg, p = 0.4), or dexmedetomidine (20.5 mcg/kg vs 24.4 mcg/kg, p = 0.5 and 42.3 mcg/kg vs 39.1 mcg/kg, p = 0.3). There was no difference in frequency of major ACE or mortality. Patients with WS received similar analgosedative medication doses compared with controls. There was no significant difference in the frequency of major ACE (including cardiac arrest, extracorporeal membrane oxygenation, and surgical re-intervention) or mortality between the two groups, though these findings must be interpreted with caution. Further investigation is necessary to elucidate the adequacy of pain/sedation control, factors that might affect analgosedative needs in this unique population, and the impact on clinical outcomes.