OBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.

Fundamento:Os defeitos cardíacos congênitos são o grupo de anormalidades estruturais mais prevalentes ao nascimento e uma das principais causas de morbidade e mortalidade infantil. Estudos têm mostrado a contribuição da variação no número de cópias na gênese das malformações cardíacas.Objetivos:Investigar a variação no número de cópias gênicas em crianças com defeito cardíaco conotruncal.Métodos:Multiplex Ligation-dependent Probe Amplification (MLPA) foi realizado em 39 pacientes com defeito cardíaco conotruncal. Avaliação clínica e laboratorial foi realizada em todos os pacientes. Os pais dos probandos que apresentaram alterações também foram investigados.Resultados:Variação no número de cópias foi detectada em 7/39 pacientes: deleção 22q11.2, duplicação 22q11.2, duplicação 15q11.2, duplicação 20p12.2, deleção 19p, duplicação 15q e 8p23.2 com duplicação 10p12.31. As características clínicas foram compatíveis com o relatado na literatura associadas com microdeleção/microduplicação encontrada. Nenhuma dessas alterações foi herdada dos pais.Conclusões:Nossos resultados demonstram que a técnica de MLPA é útil na investigação de microdeleções e microduplicações em defeitos cardíacos congênitos conotruncais. O diagnóstico precoce das variações no número de cópias em pacientes com defeito cardíaco congênito auxilia na prevenção de morbidade e diminuição da mortalidade nesses pacientes.

Background:Congenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations.Objectives:Investigate gene copy number variation (CNV) in children with conotruncal heart defect.Methods:Multiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated.Results:Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents.Conclusions:Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.

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 <0,001). De escola de inclusão, 40,7% apresentaram maior estresse; de escola especial, 69,2% (p> 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 is a multiorgan disease caused by microdeletion of 25 genes on chromosome 7 (q11.23), suggesting a vulnerability to stress. In this study we aim to determine whether children and adolescents with Williams-Beuren syndrome have high levels of stress. We studied 40 subjects of school age, with confirmed diagnosis of Williams-Beuren syndrome and control group. The instruments used: Child Stress Scale (ESI), Intelligence Scale for Children (WISC), Adult Intelligence Scale (WAIS), and a questionnaire semi-estructured. In the group with SWB, 50% had high levels of stress compared with 28.6% in the control group, statistically highly significant difference (p <0.001). In Inclusion school, 40.7% revealed higher stress; special school 69.2% (p> 0,140) difference was not statistically significant. Individuals with Williams syndrome show high level of stress. This study highlights the need for guidance about the syndrome to parents and school management, with focus on reducing of possible environmental stressors factors.

El Síndrome de Williams-Beuren es una enfermedad de múltiplos órganos causada por microdeleción de 25 genes en el cromosoma 7 (q11.23) sugiriendo una vulnerabilidad al estrés. El objetivo del estudio fue determinar si niños y adolescentes con síndrome de Williams-Beuren presentan niveles elevados de estrés. Evaluamos 40 individuos en edad escolar con diagnóstico de síndrome de Williams-Beuren y grupo control. Los instrumentos utilizados: Escala de Estrés Infantil (ESI), Escala de Inteligencia para niños (WISC), Escala de Inteligencia para Adultos (WAIS) y un cuestionario semi-estructurado. En el grupo con el SWB 50% tenían altos niveles de estrés en comparación con 28,6% en el grupo control, diferencia altamente significativa estadísticamente (p <0,001). De la escuela de inclusión 40,7% presentaron mayor estrés; de la escuela especial 69,2% (p> 0,140). Individuos con Síndrome de Williams muestran índice elevado de estrés. Este estudio destaca la necesidad de orientación sobre el síndrome a padres y gestión escolar con enfoque en la reducción de posibles factores ambientales estresantes.

INTRODUCTION: Williams-Beuren syndrome (WBS; OMIM 194050) is caused by a hemizygous contiguous gene microdeletion at 7q11.23. Supravalvular aortic stenosis, mental retardation, overfriendliness, and ocular and renal abnormalities comprise typical symptoms in WBS. Although fluorescence in situ hybridization is widely used for diagnostic confirmation, microsatellite DNA markers are considered highly informative and easily manageable. OBJECTIVES: This study aimed to test the microsatellite markers for the diagnosis of Williams-Beuren syndrome, to determine the size and parental origin of microdeletion, compare the clinical characteristics between patients with different sizes of the deletion and parental origin. METHODS: We studied 97 patients with clinical diagnosis of Williams-Beuren syndrome using five microsatellite markers: D7S1870, D7S489, D7S613, D7S2476 and D7S489_A. RESULTS AND DISCUSSION: Using five markers together, the result was informative in all patients. The most informative marker was D7S1870 (78.4%), followed by D7S613 (75.3%), D7S489 (70.1%) and D7S2476 (62.9%). The microdeletion was present in 84 (86.6%) patients and absent in 13 (13.4%) patients. Maternal deletions were found in 52.4% of patients and paternal deletions in 47.6% of patients. The observed size of deletions was 1.55 Mb in 76/ 84 patients (90.5%) and 1.84 Mb in 8/84 patients (9.5%). SVAS as well as ocular and urinary abnormalities were more frequent in the patients with a deletion. There were no clinical differences in relation to either the size or parental origin of the deletion. CONCLUSION: Using these five selected microsatellite markers was informative in all patients, thus can be considered an alternative method for molecular diagnosis in Williams-Beuren syndrome.