Williams?Beuren Syndrome with Pseudoaneurysm of Aortic Arch and Infective Vegetations for Modified Broms Procedure: Anesthetic Concerns & Echocardiographic Illustrations

Williams?Beuren syndrome is a rare genetic malformation with predilection for supravalvular aortic stenosis. Apart from cardiovascular malformation, hypocalcemia, developmental delay, and elfin facies, challenging airway make perioperative management more eventful. Association of infective endocarditis within the aortic arch and pseudoaneurysm formation is infrequent. We, hereby report a case of pseudoaneurysm formation and infective vegetation within the aortic arch in a patient with Williams syndrome and the role of transthoracic echocardiography in its perioperative management.

Fluorescence in situ hybridization (FISH) as an irreplaceable diagnostic tool for Williams-Beuren syndrome in developing countries: a literature review / Hibridização in situ fluorescente (FISH) como ferramenta diagnóstica insubstituível para a síndrome de Williams-Beuren em países em desenvolvimento: uma revisão de literatura

ABSTRACT Objective: The aim of this study was to sum up and characterize all Williams-Beuren syndrome cases diagnosed by fluorescence in situ hybridization (FISH) since its implementation, as well as to discuss FISH as a cost-effective methodology in developing countries. Data source: From January 1986 to January 2022, articles were selected using the databases in PubMed (Medline) and SciELO. The following terms were used: Williams syndrome and In Situ Hybridization, Fluorescence. Inclusion criteria included Williams-Beuren syndrome cases diagnosed by FISH with a stratified phenotype of each patient. Only studies written in English, Spanish, and Portuguese were included. Studies with overlapping syndromes or genetic conditions were excluded. Data synthesis After screening, 64 articles were included. A total of 205 individuals with Williams-Beuren syndrome diagnosed by FISH were included and further analyzed. Cardiovascular malformations were the most frequent finding (85.4%). Supravalvular aortic stenosis (62.4%) and pulmonary stenosis (30.7%) were the main cardiac alterations described. Conclusions: Our literature review reinforces that cardiac features may be the key to early diagnosis in Williams-Beuren syndrome patients. In addition, FISH may be the best diagnostic tool for developing nations that have limited access to new technologic resources.

RESUMO Objetivo: Caracterizar todos os casos de síndrome de Williams-Beuren (SWB) diagnosticados por hibridização in situ fluorescente (FISH) desde sua implementação, assim como discutir a relação custo-benefício da metodologia de FISH em países em desenvolvimento. Fontes de dados: Entre janeiro de 1986 e janeiro de 2022 foi realizada uma busca nas bases de dados PubMed (Medical Literature Analysis and Retrieval System Online — Medline) e Scientific Electronic Library Online (SciELO) usando os seguintes termos: síndrome de Williams e hibridização in situ fluorescente. O critério de inclusão utilizado foi conter a descrição detalhada de caso(s) de SWB por FISH. Apenas estudos escritos em inglês, espanhol e português foram incluídos. Trabalhos que apresentavam sobreposição de síndromes/condições genéticas foram excluídos. Síntese dos dados: Após os processos de inclusão, 64 artigos e 205 indivíduos com SWB diagnosticados por meio do método de FISH foram incluídos. O achado mais frequente entre os indivíduos foi a presença de algum tipo de malformação cardíaca (85,4%). A estenose aórtica supravalvar (62,4%) e a estenose pulmonar (30,7%) foram as alterações cardíacas mais descritas. A maioria dos estudos era proveniente dos continentes Europa, Ásia e América do Norte. Conclusões: A presente revisão de literatura reitera que as malformações cardíacas podem ser a chave para o diagnóstico precoce em pacientes com SWB. Ainda, a técnica de FISH parece ser a melhor ferramenta de diagnóstico para os países em desenvolvimento, cujo acesso às novas tecnologias ainda é escasso.

Diagnosis of one case of Williams-Beuren syndrome presenting with hypothyroidism by low-coverage massively parallel CNV sequencing / 中华内分泌代谢杂志

Objective@#To explore the clinical phenotypes and the genetic causes for a 5 years old boy with unexplained growth retardation, developmental delay, special face, and hypothyroidism.@*Methods@#Routine G-banding was performed to analyze the karyotype of the patient and his parents. In addition, whole exome sequencing and low-coverage massively parallel CNV sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs).@*Results@#The child′s karyotype was 46, XY, and his parents′ karyotypes were normal.However, CNV-seq identified a heterozygous deletion of 1.56 Mb on chromosome region 7q11.23 in the patient, including 24 protein-coding genes, which were associated with Williams-Beuren syndrome. His parents′ results of CNV-seq were normal, indicating a de novo CNVs.@*Conclusion@#A Williams-Beuren syndrome child presenting with hypothyroidism was diagnosed by CNV-seq, which would contribute to further understanding the clinical phenotypes and pathogenesis of this disease.

Williams–Beuren syndrome in Mexican patients confirmed by FISH and assessed by aCGH

Williams–Beuren syndrome (WBS) has a prevalence of 1/7500–20000 live births and results principally from a de novo deletion in 7q11.23 with a length of 1.5 Mb or 1.8 Mb. This study aimed to determine the frequency of 7q11.23 deletion, size of the segment lost, and involved genes in 47 patients with a clinical diagnosis of WBS and analysed by fluorescence in situ hybridization (FISH); among them, 31 had the expected deletion. Micro-array comparative genomic hybridization (aCGH) confirmed the loss in all 18 positive-patients tested: 14 patients had a 1.5 Mb deletion with the same breakpoints at 7q11.23 (hg19: 72726578–74139390) and comprising 24 coding genes from TRIM50 to GTF2I. Four patients showed an atypical deletion: two had a 1.6Mb loss encompassing 27 coding genes, from NSUN5 to GTF2IRD2; another had a 1.7 Mb deletion involving 27 coding genes, from POM121 to GTF2I; the remaining patient presented a deletion of 1.2 Mb that included 21 coding genes from POM121 to LIMK1. aCGH confirmed the lack of deletion in 5/16 negative-patients by FISH. All 47 patients had the characteristic facial phenotype of WBS and 45 of 47 had the typical behavioural and developmental abnormalities. Our observations further confirm that patients with a classical deletion present a typical WBS phenotype, whereas those with a high (criteria of the American Association of Pediatrics, APP) clinical scorebut lacking the expected deletion may harbour an ELN point mutation. Overall, the concomitant CNVs appeared to be incidental findings.

Oral conditions of pediatric patients with Williams-Beuren syndrome: two case reports / Condição Oral de paciente infantil com Síndrome de Williams-Beuren: dois casos clínicos

Objective: The objective of this paper was to describe the oral conditions of two children accompanied by their mothers who reported to the Department of Pediatric Dentistry of Fluminense Federal University with Williams-Beuren syndrome (WBS). Case report: The 9-year-old female patient had a family and medical history significant for placental abruption, caesarean section, delayed psychomotor development, learning disabilities, tendency to selfdistract and congenital heart disease. In contrast, the 7-year-old male patient had a normal birth and no gestational intercurrences. Discussion: Clinically, the female presented with mixed dentition, crowding in the maxillary and mandibular arches, prolonged retention of deciduous teeth, anterior and posterior cross-bite and Angle Class I malocclusion, while the male had mixed dentition and retarded psychomotor development. Due to the patients having congenital heart disease, a prophylactic antibiotic regimen was prescribed prior to the dental procedures in both of them. Conclusion: These patients had been followed up for 2 years and this case report underscores the importance of early dental evaluation and counselling for parents of WBS patients (AU)

Objetivo: O objetivo deste trabalho foi descrever as condições bucais de duas crianças acompanhadas por suas mães que relataram ao Departamento de Odontopediatria da Universidade Federal Fluminense com síndrome de Williams-Beuren (SWB). Caso clínico: Paciente do sexo feminino, 9 anos de idade, tinha história familiar de descolamento prematuro da placenta, cesariana, atraso no desenvolvimento psicomotor, dificuldades de aprendizado, tendência a auto-distribuição e cardiopatia congênita. Em contraste, o paciente de 7 anos de idade teve um parto normal e sem intercorrências gestacionais. Discussão: Clinicamente, a menina apresentava dentição mista, apinhamento nos arcos maxilar e mandibular, retenção prolongada dos dentes decíduos, mordida cruzada anterior e posterior e má oclusão de Classe I de Angle, enquanto o menino apresentava dentição mista e desenvolvimento psicomotor retardado. Devido à doença cardíaca congênita, um regime profilático de antibiótico foi prescrito antes dos procedimentos odontológicos em ambos. Conclusão: Esses pacientes foram acompanhados por dois anos e este relato de caso ressalta a importância da avaliação odontológica precoce e do aconselhamento para pais de pacientes com SWB. (AU)

Williams-Beuren Syndrome: What Orthodontists Need to Know / Síndrome de Williams-Beuren: Lo que los Ortodoncistas Deben Saber

ABSTRACT: Williams-Beuren syndrome is a rare disease with manifestations such as cardiovascular changes, distinct facial features, mental retardation, and learning disabilities. Oral manifestations are not commonly described and can often be misdiagnosed. This report describes the case of a male patient diagnosed with Williams-Beuren syndrome presenting classic clinical features that affect the face as a convex profile, with maxillary protrusion and mandibular retrusion, a discreetly acute nasolabial angle, passive labial sealing, and an open mandibular angle characteristic of Class II skeletal pattern. In addition, the patient has oral manifestations such as the absence of some dental elements, a Class II of Angle 1st division, dental cross bite, and atresic arches. The periodontal condition presents with generalized gingivitis. Knowledge about the possible manifestations of Williams-Beuren syndrome is important to improve the ability of orthodontists to better serve these patients.

RESUMEN: El síndrome de Williams-Beuren es una enfermedad rara con manifestaciones tales como cambios cardiovasculares, diversas características faciales, retraso mental y problemas de aprendizaje. Las manifestaciones orales no se describen comúnmente y con frecuencia se pueden diagnosticar erróneamente. Este informe describe el caso de un paciente masculino diagnosticado con síndrome de Williams-Beuren que presentaba características clínicas clásicas que afectaban la cara como un perfil convexo, con protrusión maxilar y retrusión mandibular, un ángulo nasolabial discretamente agudo, sellado labial pasivo y un ángulo mandibular abierto característico del patrón esquelético clase II. Además, el paciente presentaba manifestaciones orales tales como, ausencia de algunos elementos dentales, una clase II de Angle 1ª división, mordida dental cruzada y arcos acrílicos. La condición periodontal se presentaba con gingivitis generalizada. El conocimiento sobre las posibles manifestaciones del síndrome de Williams-Beuren es importante ya que mejora la capacidad de los ortodoncistas para atender mejor a estos pacientes.

Diagnosis and management of systemic hypertension due to renovascular and aortic stenosis in patients with Williams-Beuren syndrome

SUMMARY AIM To describe the incidence, diagnosis, and management of systemic arterial hypertension related to renal artery stenosis in patients with Williams-Beuren syndrome. METHODS Sixty-five patients with Williams-Beuren syndrome were evaluated for hypertension. Enrolled patients underwent Doppler sonography of the renal arteries and Doppler echocardiography. Those with Doppler sonography-detected lesions or with normal Doppler sonography but severe hypertension underwent computed tomography or gadolinium-enhanced magnetic resonance angiography of the aorta and renal vessels. Patients needing vascular therapeutic intervention underwent conventional angiography. RESULTS Systemic arterial hypertension was diagnosed in 21/65 patients with Williams-Beuren syndrome (32%; 13 male) with a mean age of 13.9 years (5mo-20yrs). In 8/21 patients renovascular hypertension was detected. Angioplasty was unsuccessful in five patients with renal artery stenosis, requiring additional treatment. Doppler echocardiography showed cardiac abnormalities in 16/21 (76%) hypertensive patients. CONCLUSION Cardiac abnormalities and hypertension in patients with Williams-Beuren syndrome are common. Thus, thorough evaluation and follow-up are necessary to reduce cardiovascular risks and mortality of these patients

RESUMO OBJETIVO Descrever a incidência, o diagnóstico e o tratamento da hipertensão arterial sistêmica relacionada com estenose da artéria renal em pacientes com síndrome de Williams-Beuren. MÉTODOS Sessenta e cinco pacientes com síndrome de Williams-Beuren foram avaliados quanto à presença de hipertensão. Os pacientes foram submetidos à ultrassonografia com Doppler das artérias renais e ecocardiograma Doppler. Aqueles com suspeita de hipertensão renovascular foram submetidos à tomografia computadorizada ou angiografia por ressonância magnética da aorta e vasos renais ou angiografia convencional. RESULTADOS A hipertensão arterial sistêmica foi diagnosticada em 21/65 pacientes com síndrome de Williams-Beuren (32%, 13 do sexo masculino), com idade média de 13,9 anos (5 meses-20 anos). Em 8/21 pacientes foi detectada a hipertensão renovascular. Angioplastia não teve sucesso em cinco pacientes com estenose da artéria renal, necessitando de tratamento adicional. O ecocardiograma Doppler mostrou anormalidades cardíacas em 16/21 (76%) pacientes hipertensos. CONCLUSÃO As anormalidades cardíacas e hipertensão arterial em pacientes com síndrome de Williams-Beuren são muito frequentes, sendo necessários uma avaliação minuciosa e seguimento para diminuir o risco cardiovascular e a morbimortalidade desses pacientes

Avaliação da influência dos sintomas clínicos na qualidade de vida de indivíduos com Síndrome de Williams-Beuren / Evaluation of the influence of clinical symptoms on the quality of life in individuals with Williams-Beuren Syndrome

Introdução: A Síndrome de Williams-Beuren (SWB) é resultado da deleção do cromossomo 7q11.23. A presença de transtornos psiquiátricos, tais como Transtorno de Ansiedade Generalizada, Déficit de Atenção e Hiperatividade, entre outros, já foram descritos nesta síndrome. Objetivo: Este estudo teve como objetivo identificar possíveis sintomas clínicos nos indivíduos com SWB e as possíveis consequências na qualidade de vida. Método: O grupo amostral com SWB constituiu-se por 20 indivíduos com idade entre 11 e 16 anos e 22 indivíduos com desenvolvimento típico (DT). Os instrumentos utilizados foram: Critério de Classificação Econômica Brasil para estimar o poder de compra das famílias urbanas; o Questionário de Capacidades e Dificuldades (SDQ), que possibilita uma medida útil em psicopatologia aplicada a crianças e jovens com 4 a 17 anos de idade; e o Questionário de Avaliação de Qualidade de Vida em Crianças e Adolescentes (AUQEI), que tem como objetivo avaliar a sensação de bem-estar mediante a opinião da própria criança e adolescente. Resultados: Os resultados sugerem que os adolescentes com SWB possuem uma boa qualidade de vida, apesar de apresentarem maiores possibilidades de sintomas psiquiátricos. Estes resultados são válidos, já que a qualidade de vida é mensurada a partir da subjetividade do indivíduo avaliado. Conclusão: Chega-se à hipótese de que os adolescentes com SWB podem apresentar uma distorção da realidade para o fator positivo/otimista, possivelmente baseada em algumas características da própria síndrome, tais como: são sempre alegres e sorridentes, fatores associados à deficiência intelectual.

Introduction: Williams-Beuren Syndrome (WBS) results from a deletion in the chromosome 7q11.23. Psychiatric symptoms, such as Generalized Anxiety Disorder (GAD), Attention Deficit Hyperactivity Disorder (ADHD), and others, have been described in this syndrome. Objective: The main purpose of this study was to identify related clinical symptoms in individuals with WBS and the impact of this disorder in their quality of life. Method: The study sample included 42 individuals aged 11 to 16 years divided into two groups: a study group composed of 20 individuals with WBS and a control group comprising 22 individuals with typical development. The following instruments were used in this evaluation: Brazilian Criterion of Economic Classification (CCEB), to estimate the purchasing power of urban households; Strengths & Difficulties Questionnaire (SDQ), to provide a useful measure of psychopathology applied to children and youth aged 4-17 years; and Quality of Life Evaluation Scale (AUQEI), to assess the feeling of well-being according to the opinion of the child and adolescent. Results: The results suggest that adolescents with WBS have a good quality of life despite presenting greater possibilities of psychiatric symptoms. These results are valid considering that quality of life is measured from the opinion of the assessed individual. Conclusion: We hypothesized that adolescents with WBS can present a distortion of reality regarding the positive/optimistic factor, possibly based on some characteristics of the syndrome such as being always cheerful and smiling, which are factors associated with intellectual disability.

A rare association of central hypothyroidism and adrenal insufficiency in a boy with Williams-Beuren syndrome

Primary hypothyroidism related to morphological and volumetric abnormalities of the thyroid gland is one of the commonest of several endocrine dysfunctions in Williams-Beuren syndrome (WBS). We report a 10-month-old boy with WBS who presented with central hypothyroidism. During the neonatal period, he had prolonged jaundice, feeding difficulties and episodes of colic that continued during early infancy. Additionally, there was slowing of growth and mild developmental delay. He underwent surgical repair for supravalvular aortic stenosis at 6 months of age. An evaluation done to exclude cortisol deficiency before initiating levothyroxine lead to the detection of secondary adrenal insufficiency, unreported previously in WBS. In addition, insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels were low. This report of hypopituitarism in WBS indicates a need for complete evaluation of pituitary dysfunction in children with WBS.

Clinical and genetic characteristics of Williams-Beuren syndrome: 2 cases report / 北京大学学报(医学版)

To explore the clinical and genetic characteristics of Williams-Beuren syndrome (WBS) and to raise awareness of the disease.The characteristics of clinical manifestations,personal history,car diac ultrasound,brain magnetic resonance imaging (MRI),electroencephalogram (EEG) and chromosome detection results of two cases with WBS were analyzed.The two patients were both male and the age was 11 months and 1 day,and 9 months and 9 days,respectively.They both suffered from cardiovascular malformation:case one presented supravalvular aortic stenosis,and case two showed atrial septal defect and patent ductus arteriosus.Both of the cases were exhibited characteristic facial features of WBS,including full orbital,spherical nose,fiat nasal bridge,long philtrum and thick lips.For the mental development,case one displayed moderate to severe developmental retardation,and case two showed severe developmental retardation.In addition,case one presented bilateral indirect inguinal hernia and hydrocele,and case two manifested feeding difficulties,buried penis and infantile spasms.Personal history:case one's mother had tocolytic therapy during pregnancy period,and case one was born at full-term by cesarean section due to amniotic fluid pollution.Supplementary examination:brain MRI of the two cases were no significant abnormalities;the EEG of case two showed hypsarrhythmia,and the epileptic spasms were recorded.Chromosome detection results:case one was identified as 7q11.23 deletion including the fragment deletion mutation of elastin (ELN) gene by multiplex ligation dependent probe amplification method,and case two was found with 7q11.21q11.23 deletion by high resolution G-band method.The two cases with WBS both had cardiovascular malformations,special facial features,mental retardation and connective tissue or urinary system abnormality.The supravalvular aortic stenosis of case one may be associated with the deletion of ELN gene,and the occurrence of epilepsy of case two may be related to the q11.21 deletion beyond the 7q11.23 region.

Endocrine dysfunctions in children with Williams-Beuren syndrome

PURPOSE: Williams-Beuren syndrome (WBS) is caused by a hemizygous microdeletion of chromosome 7q11.23 and is characterized by global cognitive impairment, dysmorphic facial features, and supravalvular aortic stenosis. Endocrine dysfunctions have been reported in patients with WBS. This study was performed to investigate the frequency, clinical features, and outcomes of endocrine dysfunctions in children with WBS. METHODS: One hundred two patients were included. The diagnosis was confirmed by chromosome analysis and fluorescent in situ hybridization. Medical charts were reviewed retrospectively to analyze endocrine dysfunctions such as short stature, precocious puberty, thyroid dysfunctions, and hypocalcemia. RESULTS: The age at diagnosis was 3.7±4.4 years (one month to 19 years). Height- and weight-standard deviation score (SDS) were -1.1±1.1 and -1.4±1.4 at presentation, respectively. Short stature was found in 26 patients (28.3%) among those older than 2 years. Body mass index-SDS increased as the patients grew older (P<0.001). Two males and one female (2.9%) were diagnosed with central precocious puberty. Nine patients (8.8%) were diagnosed with primary hypothyroidism at age 4.0±4.3 years (one month to 12.1 years); their serum thyroid stimulating hormone and free T4 levels were 15.2±5.4 µU/mL and 1.2±0.2 ng/dL, respectively. Hypercalcemia was observed in 12 out of 55 patients under age 3 (22%) at the age of 14.3±6.6 months (7 to 28 months) with a mean serum calcium level of 13.1±2.1 mg/dL. CONCLUSION: Endocrine dysfunctions are not uncommon causes of morbidity in patients with WBS. The severity and outcomes of their endocrine manifestations were heterogeneous. Long-term follow-up is needed to predict the prognosis of endocrine features.

Oral Findings and Dental Treatment in a Child with Williams-Beuren Syndrome

Williams-Beuren syndrome (WBS), also known as Williams syndrome, is a rare congenital disorder involving cardiovascular problems, mental retardation, distinctive facial features and tooth anomalies. It is caused by the submicroscopic deletion of 1.5 to 1.8 Mb on chromosome 7q11.23. This paper reports the dental care to a 7-year-old child with WBS syndrome. The interview also revealed visual impairment, sensorineural hearing loss, hyperacusis, photophobia and hoarse voice. The intraoral clinical examination showed anterior open bite, tongue thrusting, excessive interdental spacing, enamel hypomineralization of the incisors, hypoplasia and caries lesions. The dental treatment included: modulating sessions to control aversion to noises, the photophobia, and the dental fear and anxiety because of his reduced visual acuity; oral hygiene instructions, dietary and daily use of a 0.05% sodium fluoride mouthwash; the permanent mandibular left first molar was treated endodontically, and maxillary and mandibular first molars were restored with amalgam. Due to the patient's heart defect, a prophylactic antibiotic regimen was prescribed prior to the dental procedures. This patient has been followed up for 4 years and this case report underscores the importance of early dental evaluation and counseling for parents of WBS patients.

A Síndrome de Williams-Beuren (SWB), também conhecida como síndrome de Williams, consiste em uma desordem congêntica rara a qual apresenta problemas cardiovasculares, retardo mental, alterações faciais e anomalias dentárias. É causada pela microdeleção de 1,5 a 1,8 Mb no cromossomo 7q11.23. Este trabalho relata o tratamento odontológico de uma criança de 7 anos com a síndrome. Durante a anamnese constatou-se deficiência visual, perda auditiva neurossensorial, hiperacusia, fotofobia e voz rouca. O exame clínico intra-oral revelou mordida aberta anterior, deglutição atípica, espaçamento interdental excessivo, hipomineralização dos incisivos, hipoplasia e lesões de cárie. O tratamento dentário incluiu: sessões de condicionamento comportamental afim de controlar a aversão a ruídos, a fotofobia e o medo e a ansiedade frente ao tratamento odontológico, provocadas principalmente por sua reduzida acuidade visual; instruções de higiene oral, dieta e uso diário de bochechos de fluoreto de sódio a 0,05%; endodontia do primeiro molar permanente inferior esquerdo e restaurações de amálgama nos primeiros molares superiores e inferiores. Devido ao defeito cardíaco do paciente, antibioticoterapia profilática foi realizada antes dos atendimentos odontológicos. Este paciente está em acompanhamento há 4 anos e este relato ressalta a importância da avaliação odontológica precoce e do aconselhamento aos pais dos pacientes com SWB.

Sono-vigília, aspectos de memória e melatonina em Síndrome de Williams-Beuren: uma revisão de literatura / Sleep-wake, aspects of memory and melatonin in Williams-Beuren syndrome: a review of literature

A Síndrome de Williams-Beuren, distúrbio genético (microdeleção na região cromossômica 7q11.23), apresenta como fenótipo aparente habilidade social que contrasta com o mau funcionamento cognitivo global e visuo-espacial, problemas na forma receptiva, estrutural e semântica da comunicação, além de déficits na atenção, hiperatividade e na memória visuoespacial. Outra caracteristica são desordens no ciclo sono-vigília, com sono ineficaz, resistência em ir para a cama, acordares durante a noite e sonolência durante o dia. Uma possibilidade ainda não explorada nesta síndrome seria o padrão anormal na síntese de melatonina, hormônio capaz de modular a qualidade do sono. Considerando que a qualidade do sono é diretamente influenciada pelos níveis de melatonina e que tanto a melatonina quanto o sono são essenciais para o desenvolvimento adequado das funções cognitivas, buscou-se nesta revisão de literatura quais estudos investigaram separadamente e ou correlacionaram estes três aspectos (melatonina, sono-vigília e memória) na síndrome de Williams-Beuren. Para busca, foram utilizadas as bases de dados Medline/Pubmed, SciELO e Lilacs, com os seguintes descritores: "Williams Beuren syndrome, síndrome de Williams Beuren, memory, memória, sleep-wake, sono-vigília, melatonin e melatonina", por meio de cruzamento e com o conectivo AND. O levantamento bibliográfico mostrou que não existem na literatura trabalhos que correlacionaram estas três variáveis entre si nem tampouco trabalhos que investigaram a melatonina na síndrome de Williams-Beuren. As investigações sobre sono assim como as investigações sobre memória são criticamente discutidas neste trabalho que ressalta a necessidade de estudos que correlacionem estes parâmetros, bem como outros fatores comportamentais, cognitivos e bioquímicos a eles relacionados.

The Williams-Beuren syndrome (WBS), a genetic disorder caused by the hemizygous microdeletion of a region in chromosome 7q11.23 presents an apparent social skill that contrasts with the low global and visuo-spatial cognitive performance, with problems in the receptive, structural and semantic forms of communication, besides deficits in attention, hyperactivity and impairment in visuospatial memory. Another feature is disorders of the sleep-wake cycle with ineffectiveness sleep, resistance to going to bed, waking at night and drowsiness during the day. A possibility not yet explored for this disturbance would be the abnormal pattern in the hormone melatonin that modulate the sleep quality. Considering that the sleep quality is essential for the proper development of cognitive functions, the aim of this literature review was found studies that investigated separately and correlated these three aspects in Williams-Beuren syndrome: sleep-wake, memory and melatonin. In search of data was used Medline/Pubmed, SciELO and Lilacs databases, using the keywords: "Williams Beuren syndrome, memory, sleep-wake and melatonin" separately or using the connective "AND". The literature review showed that there was no studies that correlated these three aspects nor to investigated melatonin in WBS. The investigations on sleep and memory are critically discussed in this work that shows that new studies are necessary to correlate memory, sleep-wake and melatonin in WBS as well as behavioral, cognitive and biochemical aspects related to them.

Prevalence of scoliosis in Williams-Beuren syndrome patients treated at a regional reference center

OBJECTIVE: This study assessed the prevalence of scoliosis and the patterns of scoliotic curves in patients with Williams-Beuren syndrome. Williams-Beuren syndrome is caused by a chromosome 7q11.23 deletion in a region containing 28 genes, with the gene encoding elastin situated approximately at the midpoint of the deletion. Mutation of the elastin gene leads to phenotypic changes in patients, including neurodevelopmental impairment of varying degrees, characteristic facies, cardiovascular abnormalities, hypercalcemia, urological dysfunctions, and bone and joint dysfunctions. METHODS: A total of 41 patients diagnosed with Williams-Beuren syndrome, who were followed up at the genetics ambulatory center of a large referral hospital, were included in the study. There were 25 male subjects. The patients were examined and submitted to radiographic investigation for Cobb angle calculation. RESULTS: It was observed that 14 patients had scoliosis; of these 14 patients, 10 were male. The pattern of deformity in younger patients was that of flexible and simple curves, although adults presented with double and triple curves. Statistical analysis showed no relationships between scoliosis and age or sex. CONCLUSION: This study revealed a prevalence of scoliosis in patients with Williams-Beuren syndrome of 34.1%; however, age and sex were not significantly associated with scoliosis or with the severity of the curves. .

Estenosis aórtica supravalvular: reporte de caso clínico y revisión bibliográfica / Supravalvular aortic stenosis: clinical case report and review

Resumen La estenosis aórtica supravalvular es una lesión congénita obstructiva del tracto de salida del ventrículo izquierdo. Es la forma menos frecuente dentro de este grupo de lesiones, las cuales, a su vez representan el 6% de las cardiopatías congénitas en pacientes pediátricos. Esta cardiopatía se relaciona más con pacientes pediátricos, sin embargo, presentamos el caso de un paciente masculino de 23 años de edad quien acudió al hospital por haber presentado episodio de disnea súbita en reposo, acompañada de diaforesis, dolor torácico opresivo sin irradiaciones y síncope. Se realizó un ecocardiograma transtorácico con el cual se diagnosticó estenosis aórtica supravalvular.

Abstract Supravalvular aortic stenosis is a left ventricular outflow tract obstructive lesion. It is the least common form of this group of lesions, which only represents 6% of congenital heart disease in children. This condition is commonly diagnosed during childhood; however we present the case of a 23 year old man who was taken to the hospital for having presented a sudden dyspnea episode with diaphoresis, chest pain without radiation and syncope. He was diagnosed with supravalvular aortic stenosis after echocardiography.

Cognitive and behavioral heterogeneity in genetic syndromes / Heterogeneidade cognitiva e comportamental em síndromes genéticas

OBJECTIVE: this study aimed to investigate the cognitive and behavioral profiles, as well as the psychiatric symptoms and disorders in children with three different genetic syndromes with similar sociocultural and socioeconomic backgrounds. METHODS: thirty-four children aged 6 to 16 years, with Williams-Beuren syndrome (n = 10), Prader-Willi syndrome (n = 11), and Fragile X syndrome (n = 13) from the outpatient clinics of Child Psychiatry and Medical Genetics Department were cognitively assessed through the Wechsler Intelligence Scale for Children (WISC-III). Afterwards, a full-scale intelligence quotient (IQ), verbal IQ, performance IQ, standard subtest scores, as well as frequency of psychiatric symptoms and disorders were compared among the three syndromes. RESULTS: significant differences were found among the syndromes concerning verbal IQ and verbal and performance subtests. Post-hoc analysis demonstrated that vocabulary and comprehension subtest scores were significantly higher in Williams-Beuren syndrome in comparison with Prader-Willi and Fragile X syndromes, and block design and object assembly scores were significantly higher in Prader-Willi syndrome compared with Williams-Beuren and Fragile X syndromes. Additionally, there were significant differences between the syndromes concerning behavioral features and psychiatric symptoms. The Prader-Willi syndrome group presented a higher frequency of hyperphagia and self-injurious behaviors. The Fragile X syndrome group showed a higher frequency of social interaction deficits; such difference nearly reached statistical significance. CONCLUSION: the three genetic syndromes exhibited distinctive cognitive, behavioral, and psychiatric patterns. .

OBJETIVO: investigar o perfil cognitivo e comportamental, sintomas e transtornos psiquiátricos em crianças com três diferentes síndromes genéticas, com antecedentes socioculturais e socioeconômicos semelhantes. MÉTODOS: trinta e quatro crianças, entre 6 e 16 anos, com as síndromes de Williams-Beuren (n = 10), de Prader-Willi (n = 11) e do X-Frágil (n = 13), dos ambulatórios de Psiquiatria Infantil e Genética Médica, foram avaliadas cognitivamente pela Escala Wechsler de Inteligência para Crianças (WISC-III). Posteriormente, o QI total, o QI Verbal, o QI de Execução, os escores ponderados dos subtestes e a frequência de sintomas e transtornos psiquiátricos foram comparados entre as síndromes. RESULTADOS: diferenças significativas foram encontradas entre as síndromes quanto ao QI Verbal e os subtestes verbais e de execução. A análise Post-hoc demonstrou que os escores dos subtestes vocabulário e compreensão foram significativamente superiores na síndrome de Williams-Beuren em relação às síndromes de Prader-Willi e do X-Frágil, e os escores dos subtestes cubos e armar objetos foram significativamente superiores na síndrome de Prader-Willi em relação às síndromes de Williams-Beuren e do X-Frágil. Além disso, houve diferença significativa entre as síndromes quanto às características comportamentais e os sintomas psiquiátricos. O grupo com síndrome de Prader-Willi apresentou maior frequência de hiperfagia e comportamentos autolesivos. Já o grupo com síndrome do X-Frágil apresentou maior frequência do déficit da interação social. Esta diferença quase alcançou a significância estatística. CONCLUSÃO: as três síndromes genéticas ...

Estresse em crianças e adolescentes com Síndrome de Williams-Beuren em idade escolar / Stress in children and adolescents with Williams-Beuren syndrome in school age / Estrés en niños y adolescentes con síndrome de Williams-Beuren en edad escolar

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.

Detección de un caso de síndrome de Williams-Beuren por MLPA / Detection of a Williams Beuren syndrome case by MLPA

El síndrome de Williams-Beuren (WBS) es un trastorno del desarrollo neurológico que incluye diferentes manifestaciones clínicas como estenosis aórtica supravalvular, lesiones cerebrovasculares, retraso en el crecimiento, rasgos faciales "élficos" y retraso mental. Es causado por una microdeleción heterocigótica de genes contiguos en la banda cromosómica 7q11.23, generando un cambio en el número de copias (CNV) de esta región crítica. Los pacientes presentan una amplia manifestación clínica y variada expresión fenotípica. La confirmación de la sospecha clínica es esencial para el seguimiento clínico del paciente y el asesoramiento genético de la familia. La técnica estándar para la detección de WBS es la hibridización fluorescente in situ. En los últimos años la metodología MLPA (Multiplex Ligation dependent Probe Amplification) ha sido incorporada a los laboratorios diagnósticos para la detección de CNV relacionados con distintas enfermedades, incluyendo WBS. El objetivo de este trabajo fue confirmar el diagnóstico clínico de WBS en un niño, utilizando la técnica de MLPA. Los ensayos por MLPA permitieron detectar la deleción de los genes CYLN2, FZD9, STX1A, ELN, LIMK1y RFC2. En regiones geográficas donde la determinación por FISH (Fluorescence In Situ Hybridization) no está disponible para esta enfermedad, la metodología MLPA ha permitido confirmar el diagnóstico clínico y detectar los genes involucrados en la alteración. Hasta nuestro conocimiento no hay otros casos publicados sobre síndrome de WB detectado por la técnica MLPA en la Argentina.

Williams-Beuren syndrome (WBS) is a rare developmental disorder characterized by distinctive facial, neurobehavioral, and cardiovascular features. WBS is caused by a heterozygous contiguous gene microdeletion of the WBS crítical region on chromosome 7q11.23. Confirmation of clinical suspicion is essential for clinical monitoring of the patient and genetic counseling of the family. Fluorescence in situ hybridization (FISH) is considered the gold standard technique for detecting WBS. Multiplex ligation-dependent probe amplification (MLPA) has been introduced into DNA diagnostic laboratories for the detection of copy number variations in several diseases including WBS. The objective of this study was to confirm, by MLPA, the clinical diagnosis of WBS in a pediatric patient. This technique allowed to detect the deletion of CYLN2, FZD9, STX1A, ELN, LIMK1 and RFC2 genes. In geographic regions were the detection by F ISH is not available for this disease, the MLPA methodology allowed to confirm the clinic diagnostic of WBS. To our knowledge this is the first report demonstrating the confirmation of WBS by MLPA in Argentina.

Síndrome de Williams-Beuren: A propósito de un caso

Objetivo: El objetivo es dar a conocer un caso de Síndrome de Williams-Beuren (SWB). Caso Clínico: Lactante mayor, masculino de 1 año de edad, quien es remitido a la Unidad de Endocrinología del Instituto Autónomo Hospital Universitario de los Andes por presentar hipotonía y retraso en el desarrollo psicomotor. El examen físico reveló peso de 8,300 Kg (P10), talla de 75 cm (P50), potencial genético de talla de 176±10 cm. Normocéfalo, con dismorfia facial caracterizada por frente amplia, nariz corta y ancha, leve oblicuidad palpebral y epicántica, iris marrón estrellado, filtrum largo, mandíbula pequeña, labios prominentes y probable microdoncia. Además, se auscultó soplo sistólico eyectivo en foco pulmonar y el examen neurológico evidenció hipotonía troncal, leve y armónica, así como déficit de atención. El ultrasonido de tiroides reportó leve hipoplasia de la glándula, y el perfil tiroideo fue compatible con un hipotiroidismo subclínico. El estudio hemodinámico demostró la presencia de estenosis múltiple de arterias pulmonares y de ramas periféricas. Conclusiones: El paciente fue diagnosticado con SWB debido a la coexistencia de estenosis múltiple de arterias pulmonares y de ramas periféricas así como a las características faciales propias de este trastorno. Se estima que la frecuencia de este síndrome es de 1 por cada 7.500 nacidos vivos, pudiendo ser de aparición esporádica y ocurre por deleción en 7q11.23. El hipotiroidismo subclínico constituye una de las alteraciones endocrinológicas más frecuentemente encontradas en estos pacientes y se asocia a hipoplasia de la glándula tiroides.

Objective: To divulge a case of Williams-Beuren Syndrome (WBS). Clinical case: Toddler, male, 1-year old, referred to the Endrocrinology Unit of the Mérida, Venezuela Los Andes University Hospital for presenting hypotonia and psychomotor retardation. At clinical examination he exhibited:weight: 8.3 kg (P10); height: 75 cm (P50); size genetic potential: 176±10 cm; normocephalic, with facial dysmorphia characterized by broad forehead, short and wide nasal bridge, slight palpebral and epicanthic obliquity, brown starry iris, long philtrum, small jaw, bulging lips and probable microdontism. Systolic ejection murmur in pulmonic root. Neurological examination evinced slight and harmonic truncal hypotonia and attention deficit. Ultrasound reported mild thyroid hypoplasia, thyroid profile being compatible with subclinical hypothyroidism. Hemodynamic monitoring confirmed multiple stenosis of pulmonary arteries and peripheral branches. Conclusion: Patient was diagnosed with WBS because of main branch and peripheral pulmonary artery stenosis concurrent with facial demeanor typical of this disorder. Its occurrence, likely sporadic and due to 7q11.23 deletion, attends one in 7500 live births. Subclinical hypothyroidism, associated to thyroid hypoplasia, is one of the most frequent endocrinological alterations found in these patients.

Síndrome de Williams-Beuren: uma revisão da literatura / Williams-Beuren sydrome: an updated review

Introdução: A síndrome de Williams-Beuren (SWB) é uma rara síndrome de deleção de genes contíguos, sua incidência estimada é de 1: 13.000 a 1: 25.000 nativivos. A ocorrência, na maioria das famílias, é esporádica, podendo porta-se de forma autossômica dominante. Objetivo: Revisão da literatura sobre a SWB. Métodos: Foram realizadas buscas nos bancos de dados científicos eletrônicos (MEDLINE, SciELO, Lilacs, Bireme), capítulos de livros e sites de organizações voltadas para o tema SWB. Neste estudo foram examinados artigos publicados no período entre 2000 e 2011. Foram selecionados 43 artigos, dos quais 34 foram usados como base para esta revisão. Critérios de exclusão: Os artigos excluídos não tinham como tema central a SWB ou não traziam atualização relevante sobre o tema. Critérios de inclusão: Artigos e teses que tivessem como tema central a SWB, abordando os mais diversos aspectos da patologia. A coleta de dados ocorreu entre janeiro e abril 2011. As alterações físicas mais comuns são as cardiovasculares (estenose aórtica supravalvular e pulmonar periférica), fácies característica, atraso de crescimento, além das alterações comportamentais e atraso mental que, pelas suas peculiaridades, motivam especial atenção. Não se conhecem as interações gene-gene ou gene-ambiente. O diagnóstico é clínico, tendo como exame padrão-ouro o teste de Fish. É necessário o encaminhamento desses pacientes para equipes multiprofissionais. Conclusões: Conclui-se que a SWB necessita ser mais conhecida e diagnosticada pelos médicos, em especial pelos pediatras, para fins terapêuticos e de manejo adequado do paciente portador.