Talk:Williams Syndrome

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Cite this page: Hill, M.A. (2021, October 22) Embryology Williams Syndrome. Retrieved from


Congenital genitourinary abnormalities in children with Williams-Beuren syndrome

J Pediatr Urol. 2014 Feb 13. pii: S1477-5131(14)00043-6. doi: 10.1016/j.jpurol.2014.01.013. [Epub ahead of print]

Sammour ZM1, Gomes CM2, de Bessa J Jr1, Pinheiro MS3, Kim CA1, Hisano M1, Bruschini H1, Srougi M1. Author information


OBJECTIVE: Williams-Beuren syndrome (WBS) is an autosomal dominant disorder caused by a gene deletion on chromosome 7q11.23. Patients with WBS usually show a group of features such as developmental delay, cardiovascular anomalies, mental retardation, and characteristic facial appearance. Abdominal wall defects, external genitalia anomalies, and structural abnormalities of the urinary tract have been scarcely evaluated and were the focus of our study. MATERIALS AND METHODS: We prospectively evaluated 41 boys and 38 girls with WBS, with a mean age of 8.8 ± 4.1 (range 3-19 years). All patients were examined for the evaluation of inguinal and umbilical hernias and genital anomalies. All patients were offered a radiological evaluation, including urinary tract ultrasound, voiding cystourethrogram, and dimercaptosuccinic acid renal scintigraphy (DMSA scan). RESULTS: Of the 41 boys, 30 (73.1%) had abnormalities on physical examination, including bilateral undescended testis in 13 (31.7%), retractile testis in four (9.7%), hypospadias in four (9.7%), and unilateral cryptorchidism in three (7.3%) patients. Of the 38 female subjects, 17 (44.7%) had at least one abnormality, including umbilical hernia in 11 (28.9%), unilateral inguinal hernia in four (10.5%), and bilateral inguinal hernia in three (7.8%) patients. Uroradiological abnormalities were found in 41 patients (51.9%). On sonography, six (7.6%) patients had unilateral hydronephrosis, three (3.8%) had a duplicated collecting system, and two (2.5%) had kidney stones. On DMSA, performed in 36 patients, four (11.1%) had unilateral renal scarring and two (5.5%) had bilateral renal scarring. Cystourethrography was obtained from 56 patients, of whom 27 (48.2%) had bladder diverticulum, 18 (32.1%) had bladder wall trabeculation, and three (5.3%) had vesicoureteral reflux. We found no association of urological abnormalities with cardiovascular defects. CONCLUSIONS: Patients with WBS have a high prevalence of abdominal wall, external genitalia, and urological abnormalities, emphasizing the importance of proper physical examination and radiological investigation in this population. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. KEYWORDS: Bladder diverticulum, Children, Diagnostic imaging, Phenotype, Physical examination, Williams syndrome

PMID 24582571


Perceptual learning in williams syndrome: looking beyond averages

PLoS One. 2012;7(7):e40282. Epub 2012 Jul 5.

Gervan P, Gombos F, Kovacs I. Source Department of Cognitive Science, Budapest University of Technology and Economics, Budapest, Hungary.


Williams Syndrome is a genetically determined neurodevelopmental disorder characterized by an uneven cognitive profile and surprisingly large neurobehavioral differences among individuals. Previous studies have already shown different forms of memory deficiencies and learning difficulties in WS. Here we studied the capacity of WS subjects to improve their performance in a basic visual task. We employed a contour integration paradigm that addresses occipital visual function, and analyzed the initial (i.e. baseline) and after-learning performance of WS individuals. Instead of pooling the very inhomogeneous results of WS subjects together, we evaluated individual performance by expressing it in terms of the deviation from the average performance of the group of typically developing subjects of similar age. This approach helped us to reveal information about the possible origins of poor performance of WS subjects in contour integration. Although the majority of WS individuals showed both reduced baseline and reduced learning performance, individual analysis also revealed a dissociation between baseline and learning capacity in several WS subjects. In spite of impaired initial contour integration performance, some WS individuals presented learning capacity comparable to learning in the typically developing population, and vice versa, poor learning was also observed in subjects with high initial performance levels. These data indicate a dissociation between factors determining initial performance and perceptual learning.

PMID 22792262

Oxytocin and vasopressin are dysregulated in williams syndrome, a genetic disorder affecting social behavior

PLoS One. 2012;7(6):e38513. Epub 2012 Jun 12.

Dai L, Carter CS, Ying J, Bellugi U, Pournajafi-Nazarloo H, Korenberg JR. Source Center for Integrated Neuroscience and Human Behavior, and Department of Pediatrics, University of Utah, Salt Lake City, Utah, United States of America.


The molecular and neural mechanisms regulating human social-emotional behaviors are fundamentally important but largely unknown; unraveling these requires a genetic systems neuroscience analysis of human models. Williams Syndrome (WS), a condition caused by deletion of ∼28 genes, is associated with a gregarious personality, strong drive to approach strangers, difficult peer interactions, and attraction to music. WS provides a unique opportunity to identify endogenous human gene-behavior mechanisms. Social neuropeptides including oxytocin (OT) and arginine vasopressin (AVP) regulate reproductive and social behaviors in mammals, and we reasoned that these might mediate the features of WS. Here we established blood levels of OT and AVP in WS and controls at baseline, and at multiple timepoints following a positive emotional intervention (music), and a negative physical stressor (cold). We also related these levels to standardized indices of social behavior. Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. The data suggest a possible biological basis for amygdalar involvement, for increased anxiety, and for the paradox of increased approach but poor social relationships in WS. They also offer insight for translating genetic and neuroendocrine knowledge into treatments for disorders of social behaviour.

PMID 22719898


Williams syndrome is an epigenome-regulator disease

Endocr J. 2011;58(2):77-85. Epub 2011 Jan 14.

Kitagawa H, Fujiki R, Yoshimura K, Oya H, Kato S. Source Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.


A human multi-protein complex (WINAC), composed of SWI/SNF components and DNA replication-related factors, that directly interacts with the vitamin D receptor (VDR) through the Williams syndrome transcription factor (WSTF), was identified with an ATP-dependent chromatin remodeling activity. This novel ATP-dependent chromatin remodeling complex facilitates VDR-mediated transrepression as well as transactivation with its ATP-dependent chromatin remodeling activity and promoter targeting property for the activator to access to the DNA. It also suggested that in this complex, WSTF serves as a signaling sensor to receive intra-cellular singalings to switch the activity of WINAC as well as WICH, another ATP-dependent chromatin remodeling complex containing hSNF2h. By making WSTF-deficient mice, some of the heart defects as well as abnormal calcium metabolism observed in Williams syndrome are attributed to the abnormal chromatin remodeling activity caused by WSTF deficiency. Thus, we would propose to designate Williams syndrome as an epigenome-regulator disease.

PMID 21242649

Using novel control groups to dissect the amygdala's role in Williams Syndrome

Dev Cogn Neurosci. 2011 Jul;1(3):295-304.

Thornton-Wells TA, Avery SN, Blackford JU. Source Center for Human Genetics Research, Vanderbilt University Medical Center, 519 Light Hall, Nashville, TN 37232.


Williams syndrome is a neurodevelopmental disorder with an intriguing behavioral phenotype-hypersociability combined with significant non-social fears. Previous studies have demonstrated abnormalities in amygdala function in individuals with Williams syndrome compared to typically-developing controls. However, it remains unclear whether the findings are related to the atypical neurodevelopment of Williams syndrome, or are also associated with behavioral traits at the extreme end of a normal continuum. We used functional magnetic resonance imaging (fMRI) to compare amygdala blood-oxygenation-level-dependent (BOLD) responses to non-social and social images in individuals with Williams syndrome compared to either individuals with inhibited temperament (high non-social fear) or individuals with uninhibited temperament (high sociability). Individuals with Williams syndrome had larger amygdala BOLD responses when viewing the non-social fear images than the inhibited temperament control group. In contrast, when viewing both fear and neutral social images, individuals with Williams syndrome did not show smaller amygdala BOLD responses relative to the uninhibited temperament control group, but instead had amygdala responses proportionate to their sociability. These results suggest heightened amygdala response to non-social fear images is characteristic of WS, whereas, variability in amygdala response to social fear images is proportionate to, and might be explained by, levels of trait sociability.

PMID 21731599


Negative autoregulation of GTF2IRD1 in Williams-Beuren syndrome via a novel DNA binding mechanism

J Biol Chem. 2010 Feb 12;285(7):4715-24. Epub 2009 Dec 9.

Palmer SJ, Santucci N, Widagdo J, Bontempo SJ, Taylor KM, Tay ES, Hook J, Lemckert F, Gunning PW, Hardeman EC. Source Department of Anatomy, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia.


The GTF2IRD1 gene is of principal interest to the study of Williams-Beuren syndrome (WBS). This neurodevelopmental disorder results from the hemizygous deletion of a region of chromosome 7q11.23 containing 28 genes including GTF2IRD1. WBS is thought to be caused by haploinsufficiency of certain dosage-sensitive genes within the deleted region, and the feature of supravalvular aortic stenosis (SVAS) has been attributed to reduced elastin caused by deletion of ELN. Human genetic mapping data have implicated two related genes GTF2IRD1 and GTF2I in the cause of some the key features of WBS, including craniofacial dysmorphology, hypersociability, and visuospatial deficits. Mice with mutations of the Gtf2ird1 allele show evidence of craniofacial abnormalities and behavioral changes. Here we show the existence of a negative autoregulatory mechanism that controls the level of GTF2IRD1 transcription via direct binding of the GTF2IRD1 protein to a highly conserved region of the GTF2IRD1 promoter containing an array of three binding sites. The affinity for this protein-DNA interaction is critically dependent upon multiple interactions between separate domains of the protein and at least two of the DNA binding sites. This autoregulatory mechanism leads to dosage compensation of GTF2IRD1 transcription in WBS patients. The GTF2IRD1 promoter represents the first established in vivo gene target of the GTF2IRD1 protein, and we use it to model its DNA interaction capabilities.

PMID: 20007321

Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome

PLoS One. 2010 Aug 31;5(8):e12349.

Pani AM, Hobart HH, Morris CA, Mervis CB, Bray-Ward P, Kimberley KW, Rios CM, Clark RC, Gulbronson MD, Gowans GC, Gregg RG. Source Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky, United States of America.


BACKGROUND: Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.

METHODOLOGY/PRINCIPAL FINDINGS: High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.

CONCLUSIONS/SIGNIFICANCE: Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information.

PMID: 20824207


The use of 3D face shape modelling in dysmorphology

Arch Dis Child. 2007 Dec;92(12):1120-6.

[No authors listed] Abstract Facial appearance can be a significant clue in the initial identification of genetic conditions, but their low incidence limits exposure during training and inhibits the development of skills in recognising the facial "gestalt" characteristic of many dysmorphic syndromes. Here we describe the potential of computer-based models of three-dimensional (3D) facial morphology to assist in dysmorphology training, in clinical diagnosis and in multidisciplinary studies of phenotype-genotype correlations.

PMID: 18032641

Australia - Support Groups

Williams Syndrome Family Support Group of Western Australia (Inc) Williams Syndrome Association of South Australia Inc Secretary: Mr Rob Hendry Tel: (08) 9459 3716

Williams Syndrome Family Support Group of South East Queensland Rebecca Carter 15 Azalea Place Currimundi Queensland 4551 Australia Tel: (07) 5493 1185 Web:

Williams Syndrome Family Support Group (Vic) Inc. Honorary Secretary: Catherine Stenford PO Box 389 Balnarring Victoria 3926 Web:

Williams Syndrome Association of South Australia Inc. Regional Director: Amanda Strybos Contact: Amanda Strybos or Mandy Turner PO Box 247 Salisbury Adelaide 5108 Australia Tel: 8258 3867

Williams Syndrome (IHC) Association of New South Wales Dianne Petrie c/o Association of Genetic Support of Australasia Inc 66 Albion Street Surry Hills New South Wales 2021 Australia Tel: +61 2 9211 1462