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

Abstract

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.

Clinical application of chromosomal microarray analysis for the diagnosis of Williams–Beuren syndrome in Chinese Han patients

“…In our study, all patients had various degrees of physical and mental disabilities, as previously described (Hussein et al, ; Saad et al, ; Sharma et al, ). Other relatively less common findings in our study included hypothyrea/hyperthyrea, hypercalcemia, inguinal hernia, and strabismus.…”

“…Today, FISH and MLPA remain the most widely used laboratory tests for WBS diagnosis (Dutra et al, ; Hussein et al, ; Manning & Professional, ; Sharma et al, ). However, compared to FISH and MLPA, CMA is not only suitable for identifying typical/atypical CNVs and refining the distal break point for classical or nonclassical WBS, but also can identify other potential pathogenic CNVs, due to its high‐resolution and high accuracy at the whole genome level.…”

“…However, this approach is not suitable for the study of CNV due to low‐resolution and low throughput (Hussein et al, ). More recently, Multiplex ligation‐dependent probe amplification (MLPA) and chromosomal microarray analysis (CMA) have been successfully applied to detect the CNV in the 7q11.23 regions (Honjo et al, ; Li et al, ; Sharma et al, ). Exploring the underlying genetic etiology of CNV in WBS patients may provide more information about diagnosis, such as CNV length and affected genes.…”

Fluorescence in situ hybridization (FISH) as an irreplaceable diagnostic tool for Williams-Beuren syndrome in developing countries: a literature review

“…However, former standard methodologies, such as FISH, are still considered the gold standard for the detection of rare conditions, mainly in developing countries where financial support is limited and affordable technologies are preferred. 2 , 6 , 7 , 53 – 55 …”

“…57 Therefore, since all newer technologies are expensive, mainly in countries without proper research support, their use is recommended when FISH is negative in order to investigate atypical deletions. 55 The lack of medical genetic services, health facility limitations, and healthcare access restrictions are also hardships faced by developing nations. 58 Consequently, a proper evaluation by the government is needed in order to seek better healthcare services as well as improved research outcomes, mainly for patients with rare diseases such as WBS.…”