Diagnosis Of Williams-Beuren Syndrome Research Articles

Unveiling Mysteries in Congenital Diseases: A Case Report of Williams-Beuren Syndrome

Williams-Beuren syndrome (WBS) is an autosomal dominant genetic disorder closely associated with cardiovascular malformations, distinctive facial features, impaired cognitive ability, abnormal growth and development, endocrine dysfunction, and other related systems. In patients with WBS, the presence of cardiovascular malformations often necessitates genetic testing. This testing not only confirms the diagnosis but also facilitates the identification of associated syndromic features. Early and accurate diagnosis through genetic testing is instrumental for guiding further investigations, and initiating targeted therapies and support services. Such proactive management can substantially improve prognosis and quality of life for patients with WBS. Although surgery remains the most effective approach for repairing cardiovascular malformations, its implementation entails notable surgical risks. Clinicians should prioritize the identification and diagnosis of WBS, and strive to develop an effective management model involving collaboration among hospitals, families, and society. Here, we presented a case report of a patient with WBS and congenital heart disease, to contribute to a deeper understanding of this condition.

Clinical features and genetic analysis of two children with Williams-Beuren syndrome

To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS). Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed. Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3；PM2_Supporting). Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.

Prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis

BackgroundThere are a few literature reports of prenatal ultrasound manifestations of Williams-Beuren syndrome. We aimed to explore the prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis and describe the prenatal ultrasound performance of this syndrome.MethodsIn this retrospective study, we reported eight cases of Williams-Beuren syndrome diagnosed at our prenatal diagnostic center from 2016 to 2021. We systematically reviewed clinical data from these cases, including indications for invasive testing, sonographic findings, QF-PCR results, chromosomal microarray analysis results, and pregnancy outcomes.ResultsIn this study, the common ultrasound features were ventricular septal defect (37.5%), intrauterine growth retardation (25%), and aortic coarctation (25%). Moreover, all patients were found to have a common deletion in the Williams-Beuren syndrome chromosome region at the 7q11.23 locus, which contained the elastin gene. Deletion sizes ranged from 1.42 to 2.07 Mb. Seven parents asked for termination of pregnancy, and one patient was lost to follow-up.ConclusionsThis study is the most extensive prenatal study using chromosomal microarray analysis technology for detailed molecular analysis of Williams-Beuren syndrome cases. We reported three cases combined with first-reported ultrasound manifestations. Case 1 was concomitant with multicystic dysplastic kidney and duodenal atresia combined with case 3. Notably, case 4 was combined with multiple cardiovascular malformations: Tetralogy of Fallot, right aortic arch, and supravalvar aortic stenosis. These manifestations expand the intrauterine ultrasound phenotype of Williams-Beuren syndrome in previous literature reports.

Novel ophthalmic findings and deep phenotyping in Williams-Beuren syndrome

Background/AimsTo characterise the ocular manifestations of Williams-Beuren syndrome (WBS) and compare these to patients with isolated elastin mediated supravalvular aortic stenosis (SVAS).MethodsFifty-seven patients with a diagnosis of WBS and five...

An unusual combination of an atypical maternally inherited novel 0.3 Mb deletion in Williams-Beuren region and a de novo 22q11.21 microduplication in an infant with supravalvular aortic stenosis

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by supravalvular aortic stenosis (SVAS), intellectual disability, overfriendliness and dysmorphic features. It is typically caused by 1.5–1.8 Mb deletions on 7q11.23. The 22q11.21 microduplication syndrome has a variable phenotype and is frequently associated with congenital heart disease. Here we present a unique patient, carrying aberrations within both of the above syndrome regions, referred for possible diagnosis of WBS because of SVAS. The patient was a boy who died suddenly 47 days after birth, possibly due to cardiac complications. Genetic testing was carried out, including array Comparative Genomic Hybridization (aCGH), Fluorescence In situ Hybridization (FISH) and Multiplex Ligation-Dependent Probe Amplification (MLPA) showing that the proband was heterozygous for a novel and atypical 0.3 Mb deletion in WBS region (7q11.23) encompassing the ELN gene. In addition, he was found heterozygous for a 22q11.21 microduplication. Parental studies revealed that the 7q11.23 deletion was inherited from the mother who also exhibited a cardiovascular phenotype, however very mild. The same maternally inherited deletion was detected in one of the proband's siblings, born two years later with a less severe SVAS. The 22q11.2 microduplication was de novo in origin.Detection and investigation of atypical deletions within known syndrome regions are crucial for better genotype-phenotype correlations and more accurate characterization of critical regions. The combined effect of two different genetic defects – one in a known syndrome region and one with variable clinical significance, is valuable for revealing gene interactions and enabling more accurate predictions, especially in prenatal diagnosis.

Endocrine manifestations in children with Williams-Beuren syndrome.

Endocrine abnormalities in Williams-Beuren syndrome (WBS) include growth retardation, precocious puberty, hypercalcaemia and thyroid disorders. We aimed to characterise these abnormalities in a national cohort of children with WBS. A retrospective study comprising a national cohort of individuals with WBS in Israel (16 males, 18 females) followed between 2010 and 2016. The age at diagnosis of WBS was 1.4±1.0years. Height standard deviation score (SDS) at last visit was correlated with the midparental height SDS (r=0.46 p=0.007). Yet, participants did not reach their midparental height, with a difference of 1.40±0.85SD (p<0.001). Short stature below the 3rd percentile was found in 14 participants (41%). Mean insulin-like growth factor 1 SDS was low (-0.61±1.64) and was correlated with the mean height SDS (r=0.63 p=0.038). Two participants were diagnosed with growth hormone deficiency, and initiation of growth hormone treatment improved their height velocity. A total of eight participants (23.5%) had mild hypercalcaemia, five girls (14.7%) had precocious puberty and five participants (14.7%) had thyroid abnormalities. Individuals with WBS had a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Precocious puberty, hypercalcaemia and thyroid abnormalities should be screened for and treated as needed.

Williams-Beuren Syndrome With Primary Hyperparathyroidism: A Rare Diagnosis In A Rare Genetic Syndrome

ABSTRACT Objective: This case report is the first to describe functional parathyroid disease in Williams-Beuren Syndrome (WBS). We report a patient with hypercalcemia in infancy and later in adulthood whose unusual complex of elfin facies and multiple medical comorbidities, including hypercalcemia, ultimately led to a diagnosis of WBS by fluorescent in situ hybridization. While hypercalcemia is a common finding in patients with WBS, parathyroid hormone levels are typically suppressed. Methods: This study consists of a case report and literature review conducted in a high-volume university endocrine surgery center. We describe a 58-year-old patient with elfin facies, recurrent hyperparathyroidism, friendly personality, cognitive impairment, recurrent cystitis, hypertension, and stroke who was treated surgically for primary hyperparathyroidism with durable cure of his hypercalcemia. Outcomes are measured with long-term biochemical confirmation of cure after several re-operative surgical interventions. Resul...

Estresse em crianças e adolescentes com Síndrome de Williams-Beuren em idade escolar

Síndrome de Williams-Beuren é uma doença de múltiplos órgãos causada por microdeleção de 25 genes no cromossomo 7 (q11.23), sugerindo uma vulnerabilidade ao estresse. Objetivamos determinar se crianças e adolescentes com síndrome de Williams-Beuren apresentam níveis elevados de estresse. Avaliamos 40 indivíduos em idade escolar, com diagnóstico de síndrome de Williams-Beuren e grupo controle. Os instrumentos utilizados: Escala de Estresse Infantil (ESI), Escala de Inteligência para Crianças (WISC), Escala de Inteligência para Adultos (WAIS) e um questionário semiestruturado. No grupo com o SWB, 50% tinham altos níveis de estresse em comparação com 28,6% no grupo controle, diferença altamente significativa estatisticamente (p &lt;0,001). De escola de inclusão, 40,7% apresentaram maior estresse; de escola especial, 69,2% (p&gt; 0,140). Indivíduos com síndrome de Williams mostram índice elevado de estresse. Este estudo destaca a necessidade de orientação sobre a síndrome a pais e gestão escolar, com foco na redução de possíveis fatores ambientais estressantes.

Williams-Beuren syndrome: Usual face, unusual heart

Williams-Beuren Syndrome (WB-S) occurs in approximately 1/7500 live births. It is characterized by typical facial features, congenital heart defects and mild mental retardation. Around 75% - 80% of all patients have some kind of cardiovascular disorder being supravalvular aortic stenosis and pulmonary artery stenosis the most frequent. This syndrome is due to a contiguous gene deletion (1- to 2-megabase deletion on the long arm of chromosome 7), including the entire elastin gene and 20 additional genes. We present a case of a two year old boy with WB-S and Tetralogy of Fallot, a very infrequent association. Diagnosis of WB-S could be made because of typical facial features. Characteristic WB-S deletion was present. Genetic study to rule out 22q11 deletion was also performed.

Behavioral features of Williams Beuren syndrome compared to Fragile X syndrome and subjects with intellectual disability without defined etiology

Williams-Beuren syndrome (WBS) is a genetically determined neurodevelopmental disorder caused by a heterozygous deletion of 26–28 genes on chromosome band 7q11.23. During the past few years, researchers and clinicians have significantly contributed to define the phenotype of the syndrome, including its cognitive and behavioral aspects. However, it is not well known yet whether the psychological problems are specific to the syndrome or secondary to the intellectual disability (ID). The aim of our study was to better define the psychopathological profile of WBS and whether or not it is related with IQ or anxiety symptoms. Twenty-five subjects (12 girls, 13 boys) with a diagnosis of WBS were compared to 27 boys with Fragile X Syndrome and to 24 boys with ID of non-specific etiology using the Child Behavior Checklist. Anxiety, depression and attention problems were the main behavioral problems found in WBS with no gender differences. Significant differences between cohorts were observed in somatic complaints, delinquent behavior, aggressive behavior, and externalizing problems. Some associations between IQ and anxiety items were found. The findings are discussed in terms of behavioral phenotypes, genetic implications and ID.

Infantile Spasms in Individuals with Williams-Beuren Syndrome are Associated with Deletion of the MAG12 Gene on Chromosome 7q11.23-7q21.11

Infantile Spasms in Individuals with Williams-Beuren Syndrome are Associated with Deletion of the MAG12 Gene on Chromosome 7q11.23-7q21.11

Fente palatine et syndrome de Williams

Cleft palate is not one of the malformations in the Williams-Beuren syndrome. We report the case of a female patient affected by Williams syndrome, presenting with a cleft palate. The diagnosis of Williams-Beuren syndrome was confirmed by genetic analysis. Cleft palate with a Williams syndrome can be fortuitous given these two affections' frequency. The prevalence of Williams syndrome is 1/7500 to 1/10,000 births and palatine division 1/2000 to 1/2500. Cleft palate might also be a rare entity of Williams syndrome. We cannot be sure that the two are linked.

Analysis of Clinical Features of Williams-Beuren Syndrome Referred for Molecular Cytogenetic Study

Objective: Williams-Beuren syndrome (WBS) is a contiguous gene deletion disorder in which the commonly deleted region encompasses about 1.5~2.0 Mb of DNA at 7q11.23. Clinical features of WBS change with age and vary between patients. We attempted to establish useful indicators for clinical recognition of WBS in infancy and childhood. Materials and Methods: We analyzed the clinical characteristics of 25 patients referred to us to confirm a diagnosis of WBS. Those 25 patients were classified into 3 groups: group 1, younger than 3 years; group 2, between 3 and 5 years old; and group 3, older than 5 years. A diagnosis was made by fluorescence in situ hybridization (FISH) analysis. Results: Nineteen of the 25 suspected cases (76%) were found to have deletion of the elastin gene. Nine of the 14 patients in group 1 (64.29%) had the deletion as did 5 in 6 in group 2 (83.33%) and 5 in 5 (100%) in group 3. Seventy-two percent (18/25) of patients with deletion of the elastin gene had congenital cardiovascular defects and developmental delay, 68% (17/25) had dysmorphic features, 56% (14/25) had mental retardation, 40% (10/25) had a gregarious personality, 28% (7/25) had dental abnormalities in, 4% (1/25) had strabismus, 4% (1/25) had systemic hypertension. Most of the cases (19/25) with more than 2 phenotypic features were found to have deletion of the elastin gene, particularly those with cardiovascular defects. Conclusions: The clinical characteristics, including SVAS/PPS, mental retardation, developmental delay, a dysmorphic face, dental abnormalities, and a gregarious personality may be useful indicators of WBS. Although cardiovascular defects alone cannot serve as an absolute indicator, the combination of cardiovascular defects with 1 of the other phenotypic features can help make a diagnosis of WBS.