A Distance-Delivered Social Skills Program for Young Adults with Williams Syndrome: Evaluating Feasibility and Preliminary Efficacy.

Adults with Williams syndrome (WS) display hypersocial behaviors and experience social skills deficits. To improve social outcomes, we evaluated the feasibility, acceptability, and preliminary efficacy of an 8-week distance-delivered social skills program for adults with WS. Sessions were offered twice a week for 90 min. Twenty-four adults with WS were assigned to an intervention or waitlist control group. Outcomes were assessed through interviews and surveys with adults with WS, parents, and facilitators. The intervention was rated as acceptable and feasible by all. Parents rated adults with WS as displaying significant improvements in social skills; yet ratings by adults with WS did not change. Adults also displayed increased social skills knowledge following participation. Implications for practice and future research are discussed.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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.

Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing.

Blended phenotypes exhibited by a patient may present a challenge to the establishment of diagnosis. In this study, we report a seven-year-old Murut girl with unusual features of Williams-Beuren syndrome (WBS), including recurrent infections and skin abscesses. Considering the possibility of a second genetic disorder, a mutation screening for genes associated with inborn errors of immunity (IEI) was conducted using whole exome sequencing (WES). Analysis of copy number variations (CNVs) from the exome data revealed a 1.53Mb heterozygous deletion on chromosome 7q11.23, corresponding to the known WBS. We also identified a biallelic loss of NCF1, which indicated autosomal recessive chronic granulomatous disease (CGD). Dihydrorhodamine (DHR) flow cytometric assay demonstrated abnormally low neutrophil oxidative burst activity. Coamplification of NCF1 and its pseudogenes identified a GT-deletion (ΔGT) at the start of exon 2 in NCF1 (NM_000265.7: c.75_76delGT: p.Tyr26Hisfs*26). Estimation of NCF1-to-NCF1 pseudogenes ratio using ΔGT and 20-bp gene scans affirmed nil copies of NCF1 in the patient. While the father had a normal ratio of 2:4, the mother had a ratio of 1:5, implicating the carrier of ΔGT-containing NCF1. Discovery of a 7q11.23 deletion involving one NCF1 allele and a ΔGT in the second NCF1 allele explained the coexistence of WBS and CGD in our patient. This study highlights the capability of WES to establish a molecular diagnosis for a case with blended phenotypes, enabling the provision of appropriate prophylactic treatment.

Health Care Supervision for Children With Williams Syndrome.

This set of recommendations is designed to assist the pediatrician in caring for children with Williams syndrome (WS) who were diagnosed by using clinical features and with chromosome 7 microdeletion confirmed by fluorescence in situ hybridization, chromosome microarray, or multiplex ligation-dependent probe amplification. The recommendations in this report reflect review of the current literature, including previously peer-reviewed and published management suggestions for WS, as well as the consensus of physicians and psychologists with expertise in the care of individuals with WS. These general recommendations for the syndrome do not replace individualized medical assessment and treatment.

Williams syndrome: recent advances in our understanding of cognitive, social and psychological functioning.

PURPOSE OF REVIEW: Since the last review of Williams syndrome in Current Opinion (2001) there have been many advances in knowledge about the cognitive, social and psychological impairments that characterize the disorder. The present review focuses on current research in these areas. RECENT FINDINGS: Williams syndrome is associated with a wide range of cognitive, linguistic, social and other difficulties. When young, these deficits may appear relatively mild - for example, many children are highly sociable and talkative - but with age the impact of these difficulties becomes more evident. Thus, inappropriate social behaviours can significantly increase the risk of social exclusion and vulnerability to abuse. Their superficially good speech can lead to educational and other services failing to understand the true extent of impairments or the need for specialist support. Mental health problems, especially related to anxiety, often become an increasing challenge from adolescence onwards. SUMMARY: The core difficulties associated with Williams syndrome have a cascading effect on many areas of development over time. However, specialist provision is rare and intervention trials are almost nonexistent. Longitudinal research is needed to identify factors associated with cognitive, social and emotional problems and to develop more effective ways of minimizing and treating difficulties.

Ortodoncia con sistema de alineación con placas en pacientes con discapacidad / Orthodontics with plate aligning system in disabled patients

En personas con discapacidad se presentan las enfermedades prevalentes de la cavidad bucal con mayor frecuencia. Dentro de éstas, las alteraciones oclusales, como el apiñamiento dentario, son muy frecuentes y se considera responsable de exacerbar la patología gingival, periodontal y la estética, con impacto en la salud bucodental y la calidad de vida de estos pacientes. La técnica basada en el uso de placas alineadoras es sencilla, no invasiva y fundamentalmente preventiva de la enfermedad buco-dental (AU)

An Update on Common Chromosome Microdeletion and Microduplication Syndromes.

This review summarizes common microdeletion and microduplication syndromes and highlights important updates in patient-care needs for people with these conditions (22q11.2, 7q11.23, 17p11.2, and 16p11.2). These conditions are in chromosomal "hotspots" and have an estimated prevalence of 1 in 1,000 to 1 in 25,000. Some conditions have possible increased or decreased genetic risk of schizophrenia (22q11.2 deletion and duplication), or risk of aortic dilation (7q11.23 duplication) versus aortic stenosis (7q11.23 deletion). Many of these conditions are associated with developmental delay, autism, and/or multiple congenital anomalies and would not be detected with a karyotype. Chromosomal microarray analysis will detect all these conditions with a single screening test, allowing for the appropriate diagnosis and management of these patients. [Pediatr Ann. 2018;47(5):e198-e203.].

Addressing the Educational Needs of Children with Williams Syndrome: A Rather Neglected Area of Research?

Williams syndrome (WS) is a rare neurodevelopmental disorder associated with physical health problems, limitations in cognitive abilities and increased risk of mental health difficulties. This profile of complex needs may make it challenging to support children with WS in schools. Surprisingly, in the current international move for inclusion, limited research exists on the educational provision and academic achievements of children with WS, including the non-existing literature on their voices and the perspectives of key stakeholders. This letter calls for additional research on the risk and protective factors associated with the educational outcomes of these children, the perspectives of the children themselves and the development of the evidence-base about the effectiveness of education intervention programs.

Delineation of a spatial working memory profile using a non-verbal eye-tracking paradigm in young children with autism and Williams syndrome.

Working memory deficits profoundly inhibit children's ability to learn. While deficits have been identified in disorders such as autism spectrum disorder (ASD) and Williams syndrome (WS), findings are equivocal, and very little is known about the nature of these deficits early in development. A major barrier to advances in this area is the availability of tasks suitable for young children with neurodevelopmental disorders who experience difficulties with following verbal instructions or who are distressed by formal testing demands. To address these issues, a novel eye-tracking paradigm was designed based on an adaptation of the classic A not B paradigm in order to examine the early foundations of spatial working memory capabilities in 26 developmentally delayed preschool children with ASD, 18 age- and IQ-matched children with WS, and 19 age-matched typically-developing (TD) children. The results revealed evidence that foundational spatial working memory performance in ASD and WS was comparable with that of TD children. Performance was associated with intellectual ability in the ASD and TD groups, but not in the WS group. Performance was not associated with adaptive behavior in any group. These findings are discussed in the context of previous research that has been largely limited to older and substantially less developmentally delayed children with these neurodevelopmental disorders.

[Association between Williams syndrome and adrenal insufficiency]. / Association syndrome de Williams et insuffisance surrénalienne.

Williams syndrome is a developmental disorder including dysmorphia, cardiovascular malformations and a specific neuropsychological profile together with other associated disorders. We report the case of a 17-year old girl, born of a non-inbred marriage, with Williams syndrome discovered during an assessment of degree of failure to thrive. Its association with primary adrenal insufficiency makes it unique. Diagnosis is confirmed by cytogenetic and molecular analysis. Its management consists of the implementation of treatment for adrenal insufficiency associated with a clinico-biological monitoring.

Peri-procedural risk stratification and management of patients with Williams syndrome.

Williams syndrome (WS) is a congenital, multisystem disorder affecting the cardiovascular, connective tissue, and central nervous systems in 1 in 10 000 live births. Cardiovascular involvement is the most common cause of morbidity and mortality in patients with WS, and noninvasive and invasive procedures are common. Sudden cardiovascular collapse in patients with WS is a well-known phenomenon, especially in the peri-procedural period. Detailed guidelines for peri-procedural management of patients with WS are limited. The goal of this review is to provide thoughtful, safe and effective management strategies for the peri-procedural care of patients with WS with careful consideration of hemodynamic impacts of anesthetic strategies. In addition, an expanded risk stratification system for anesthetic administration is provided.

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.

Parent and Self-Report Ratings on the Perceived Levels of Social Vulnerability of Adults with Williams Syndrome.

The current study took a multi-informant approach to compare parent to self-report ratings of social vulnerability of adults with Williams syndrome (WS). Participants included 102 pairs of adults with WS and their parents. Parents completed the Social Vulnerability Questionnaire and adults with WS completed an adapted version of the questionnaire. Parents consistently reported higher levels of social vulnerability for their son/daughter than the individual with WS reported, with the exception of emotional abuse. The lower ratings of social vulnerability by adults with WS, compared to their parents, offer new information about their insight into their own vulnerability. These findings highlight the importance of teaching self-awareness as a part of a multi-informant approach to interventions designed to target social vulnerability.

Description of common musculoskeletal findings in Williams Syndrome and implications for therapies.

Williams syndrome (WS), also referred to as Williams-Beuren syndrome (WBS), is a relatively rare genetic disorder affecting ∼1/10,000 persons. Since the disorder is caused by a micro-deletion of ∼1.5 Mb, it is not surprising that the manifestations of WS are extremely broad, involving most body systems. In this paper, we primarily focus on the musculoskeletal aspects of WS as these findings have not been the subject of a comprehensive review. We review the MSK features commonly seen in individuals with WS, along with related sensory and neurological issues interacting with and compounding underlying MSK abnormalities. We end by providing perspective, particularly from the vantage point of a physical therapist, on therapeutic interventions to address the most common MSK and related features seen in WS. Clin. Anat. 29:578-589, 2016. © 2016 Wiley Periodicals, Inc.

Malassezia Pneumonia: A Rare Complication of Parenteral Nutrition Therapy.

Malassezia species (formerly known as Pityrosporum) are part of normal human skin flora and have been associated with benign dermatologic conditions, such as seborrheic dermatitis and tinea versicolor. In rare cases, however, Malassezia has been associated with systemic disease in immunocompromised patients and infants in the neonatal intensive care unit. Malassezia species require long-chain fatty acids for growth and therefore have a known predilection for individuals receiving lipid containing intravenous parenteral nutrition (PN). Systemic infections are characterized by prolonged fevers and illness but can include nonspecific signs and symptoms. We present the diagnosis and management of a rare case of an immunocompetent, nonneonatal, PN-dependent child with Malassezia furfur pneumonia.

Risk assessment and anesthetic management of patients with Williams syndrome: a comprehensive review.

Since the first description in 1961, several case reports have documented an increased incidence of anesthesia-related cardiac arrest in patients with Williams-Beuren syndrome, commonly known as Williams syndrome (WS). Widespread arteriopathy secondary to an elastin gene defect results in various cardiac defects, including supravalvar aortic stenosis (SVAS) and coronary artery anomalies, which can increase the risk of myocardial ischemia. Even though patients with WS are known to have increased risk of adverse events during anesthesia and sedation, they often undergo several procedures that require anesthesia during their lifetimes, and cases of perianesthetic cardiac arrest continue to be reported. To date, no prospective studies have been reported that quantify anesthetic risk in individual patients with WS. In this article, we review the clinical manifestations of WS, propose a consensus, expert-informed method to estimate anesthetic risk based on the current literature, and provide recommendations for periprocedural management of this patient population.

Intracisternal Gtf2i Gene Therapy Ameliorates Deficits in Cognition and Synaptic Plasticity of a Mouse Model of Williams-Beuren Syndrome.

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of 26-28 genes at chromosome band 7q11.23. Haploinsufficiency at GTF2I has been shown to play a major role in the neurobehavioral phenotype. By characterizing the neuronal architecture in four animal models with intragenic, partial, and complete deletions of the WBS critical interval (ΔGtf2i(+/-), ΔGtf2i( -/-), PD, and CD), we clarify the involvement of Gtf2i in neurocognitive features. All mutant mice showed hypersociability, impaired motor learning and coordination, and altered anxiety-like behavior. Dendritic length was decreased in the CA1 of ΔGtf2i(+/-), ΔGtf2i ( -/-), and CD mice. Spine density was reduced, and spines were shorter in ΔGtf2i ( -/-), PD, and CD mice. Overexpression of Pik3r1 and downregulation of Bdnf were observed in ΔGtf2i(+/-), PD, and CD mice. Intracisternal Gtf2i-gene therapy in CD mice using adeno-associated virus resulted in increased mGtf2i expression and normalization of Bdnf levels, along with beneficial effects in motor coordination, sociability, and anxiety, despite no significant changes in neuronal architecture. Our findings further indicate that Gtf2i haploinsufficiency plays an important role in the neurodevelopmental and cognitive abnormalities of WBS and that it is possible to rescue part of this neurocognitive phenotype by restoring Gtf2i expression levels in specific brain areas.

Late-onset hypercalcemia in Williams-Beuren syndrome: importance of early and frequent screening and intervention.

Williams-Beuren syndrome (WBS) affects multiple systems and has a known association with infantile hypercalcemia that is typically mild and transient. We report a 12-month-old female previously diagnosed with WBS by a chromosomal microarray, who was admitted for failure to thrive. Upon evaluation, serum calcium of 19.0 mg/dL (4.75 mmol/L) (normal 9-11 mg/dL, SI: 2.25-2.75 mmol/L) and serum ionized calcium of 2.33 mmol/L (normal 1.22-1.37 mmol/L) were revealed. Her hypercalcemia correlated with symptoms of irritability, poor feeding, mild hypotonia, and constipation, which were increasingly present for 6 months prior to admission. This calcium level is one of the highest reported in association with WBS. Additionally, while hypercalcemia associated with WBS typically resolves by the first year, this case represents a later presentation as compared to other reports. The patient initially responded to conservative treatment with intravenous fluids administration, loop diuretic therapy, and dietary calcium restriction. However, she subsequently had rebound hypercalcemia 5 weeks after treatment and received one dose of intravenous bisphosphonate with subsequent resolution of her hypercalcemia. Our report highlights the importance of screening, early management, and recognition of late presentation hypercalcemia in the setting of WBS.