Williams-Beuren Syndrome: A Clinical Study of 55 Brazilian Patients and the Diagnostic Use of MLPA

Rachel Sayuri Honjo,Erika Arai Furusawa,Leslie Domenici Kulikowski,Chong Ae Kim,Evelin Aline Zanardo,Roberta Lelis Dutra,Larissa Sampaio de Athayde Costa,Debora Romeo Bertola

doi:10.1155/2015/903175

Abstract

Williams-Beuren syndrome (WBS) is a genetic disease caused by a microdeletion in the 7q11.23 region. It is characterized by congenital heart disease, mainly supravalvular aortic stenosis, mental retardation, mild short stature, facial dysmorphisms, and variable abnormalities in different systems. Objectives. To report the clinical findings of 55 Brazilian patients confirmed by multiplex ligation-dependent probe amplification (MLPA). Methods. Patients were followed up for 4 years at the Genetics Unit of the Instituto da Criança of the Hospital das Clínicas, FMUSP, Brazil. A kit specific for WBS was used to detect the 7q11.23 microdeletion. Results. Two patients with negative FISH results had positive MLPA results for WBS. The characteristics of the patients with the deletion were as follows: typical WBS facies (98.2%), neuropsychomotor delay (98.2%), hypersocial behavior (94.5%), hyperacusis (94.5%), and congenital heart disease (81.8%). Conclusions. MLPA was effective in detecting the microdeletion in the 7q11.23 region to confirm the diagnosis of WBS. MLPA was also able to confirm the diagnosis of WBS in two patients with typical clinical characteristics but negative FISH results. Thus, MLPA is a promising method in the diagnostic investigation of WBS. WBS is a multisystemic disorder and therefore requires multidisciplinary care and specific follow-up to prevent complications.

Highlights

Williams-Beuren syndrome (WBS) is a genetic multisystemic disease characterized by congenital heart disease, mainly supravalvular aortic stenosis (SVAS), mental retardation, mild short stature, facial dysmorphisms, and variable abnormalities in the genitourinary, endocrinological, ophthalmological, and skeletal systems [1, 2]
The typical facial dysmorphisms found in WBS are as follows: high forehead, medial broadening of the eyebrows, periorbital fullness, depressed nasal bridge, malar hypoplasia, thick lips, and long nasolabial philtrum [1, 2, 5]
The assessment and long follow-up of WBS patients by several medical specialties is of great relevance due to the relatively high prevalence of multisystem manifestations and complications

Summary

Introduction

Williams-Beuren syndrome (WBS) is a genetic multisystemic disease characterized by congenital heart disease, mainly supravalvular aortic stenosis (SVAS), mental retardation, mild short stature, facial dysmorphisms, and variable abnormalities in the genitourinary, endocrinological, ophthalmological, and skeletal systems [1, 2]. Short stature is common [6] but not severe. Several studies report that patients with WBS have unique cognitive and behavioral profiles, with characteristic dissociations among different domains, such as better skills in language and deficits in motor and visuospatial activities [7,8,9]. Patients have characteristic hypersocial behavior, even with strangers [10, 11]

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Discussion

Conclusion