Clinical Manifestations and Molecular Investigation of 50 Patients with Williams Syndrome in the Greek Population

Amenta, Styliani; Sofocleous, Christalena; Kοlialexi, Aggeliki; Thomaidis, Loretta; Giouroukos, S.; Karavitakis, Emmanuel; Mavrou, Ariadni; Kitsiou, Sofia; Kanavakis, Emmanuel; Fryssira, Helen

doi:10.1203/01.pdr.0000157675.06850.68

Cited by 44 publications

(47 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Puberty typically occurs early and is associated with abbreviated pubertal growth spurt in both genders (Pankau et al 1992;Partsch et al 1999). Central precocious puberty has been reported in about 15% of WBS girls (Amenta et al 2005;Ferrero et al 2007;Partsch et al 2002). Growth should be carefully monitored as failure to thrive may result from hypothyroidism or celiac disease, which have both increased prevalence in WBS.…”

Section: Facial Characteristicsmentioning

confidence: 99%

See 1 more Smart Citation

Copy number variants at Williams–Beuren syndrome 7q11.23 region

et al. 2010

View full text Add to dashboard Cite

Copy number variants (CNVs) of the Williams-Beuren syndrome (WBS) 7q11.23 region are responsible for neurodevelopmental disorders with multi-system involvement and variable expressivity. Typical features of WBS microdeletion comprise a recognizable pattern of facial dysmorphisms, supravalvular aortic stenosis, connective tissue abnormalities, hypercalcemia, and a distinctive neurobehavioral phenotype. Conversely, the phenotype of patients carrying the 7q11.23 reciprocal duplications includes less distinctive facial dysmorphisms and prominent speech delay. The common deletion/duplication ranges in size from 1.5 to 1.8 Mb and encompasses approximately 28 genes. This region is flanked by low copy repeats (LCRs) with greater than ~97% identity, which can mediate non-allelic homologous recombination resulting from misalignment of LCRs during meiosis. A clear genotype-phenotype correlation has been established in WBS only for the elastin gene, which is responsible for the vascular and connective tissue abnormalities. The molecular substrates underlying the other clinical features of 7q11.23 CNVs, including the neurocognitive phenotypes, are still debated. Recent studies suggest that besides the role of the genes in the deleted/duplicated interval, multiple factors such as regulatory sequences, epigenetic mechanisms, parental origin of the CNV, and nucleotide variations in the non-deleted/duplicated allele may be important in determining the variable expressivity of 7q11.23 CNV phenotypes. Here, we review the clinical and molecular findings and the recent insights on genomic disorders associated with CNVs involving the 7q11.23 region.

show abstract

Section: Facial Characteristicsmentioning

confidence: 99%

“…Although it was recognized early as a feature of WBS (Black and Carter 1963), transient hypercalcemia is documented only in a minority (6-15%) of patients (American Academy of Pediatrics Committee on Genetics 2001; Amenta et al 2005;Ferrero et al 2007).…”

Section: Facial Characteristicsmentioning

confidence: 99%

Copy number variants at Williams–Beuren syndrome 7q11.23 region

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The prevalence of CV abnormalities in 423 patients from nine selected international series published in the last two decades is shown in Table 1 (36)(37)(38)(39)(40)(41)(42)(43)(44). Many patients have multiple CV clinical findings.…”

Section: Clinical Features Of Wbsmentioning

confidence: 99%

“…The series from Table 1 describe operative or catheter-based interventions in 18% of patients for left ventricular outflow tract obstruction and in 4% of patients for right ventricular outflow tract obstruction (36)(37)(38)(39)(40)(41)(42)(43)(44). Patients with mild SVAS in infancy (peak catheterization gradient <20 mmHg) often remain stable and do not require intervention (36).…”

Section: Current Treatmentmentioning

confidence: 99%

Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome

Pober¹,

Johnson²,

Urban³

2008

J. Clin. Invest.

179

160

View full text Add to dashboard Cite

“…It has been reported to occur in 5-50% [Pérez Jurado et al, 1996;Amenta et al, 2005] of patients with WBS. Renal function evaluation was available for 20 cases, and 4 of them showed the presence of renal abnormalities such as medullary nephrocalcinosis and vesicoureteral reflux.…”

Section: Discussionmentioning

confidence: 99%

Williams-Beuren Syndrome: Experience of 43 Patients and a Report of an Atypical Case from a Tertiary Care Center in India

Sharma

Gupta

Chowdhury

et al. 2015

Cytogenet Genome Res

View full text Add to dashboard Cite

Williams-Beuren syndrome (WBS) or Williams syndrome (OMIM 194050) is a multisystem disorder manifested by neurodevelopmental delay and is caused by a hemizygous deletion of ∼1.5-1.8 Mb in the 7q11.23 region. Clinical features include cardiovascular anomalies (mainly supravalvular aortic stenosis), peripheral pulmonary stenosis, distinctive facies, intellectual disability (usually mild), unique personality characteristics, and growth and endocrine abnormalities. Clinical diagnostic criteria are available for WBS; however, the mainstay of diagnosis is the detection of the contiguous gene deletion. Although FISH remains the most widely used laboratory test, the diagnosis can also be established by means of qPCR, MLPA, microsatellite marker analysis, and chromosomal microarray (CMA). We evaluated the utility of MLPA to detect deletion/duplication in the 7q11.23 region in 43 patients suspected to have WBS using MLPA kits for microdeletion syndromes. A hemizygous deletion in the 7q11.23 region was found in 41 (95.3%) patients using MLPA. One patient had an atypical deletion detected by CMA. During the initial period of this study, the results of 12 patients tested by MLPA were also confirmed by FISH. Compared to FISH and CMA, MLPA is a cheaper, high-throughput, less labor-intensive and less time-consuming technique for the diagnosis of WBS. Although CMA is expensive and labor-intensive, its effectiveness is demonstrated to detect an atypical deletion and to delineate the breakpoints.

show abstract

Clinical Manifestations and Molecular Investigation of 50 Patients with Williams Syndrome in the Greek Population

Cited by 44 publications

References 67 publications

Copy number variants at Williams–Beuren syndrome 7q11.23 region

Copy number variants at Williams–Beuren syndrome 7q11.23 region

Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome

Williams-Beuren Syndrome: Experience of 43 Patients and a Report of an Atypical Case from a Tertiary Care Center in India

Contact Info

Product

Resources

About