Nationwide questionnaire data of 229 Williams-Beuren syndrome patients using WhatsApp tool / Resultados de um questionário nacional de 229 pacientes com síndrome de Williams-Beuren obtidos por WhatsApp

ABSTRACT Background: Williams-Beuren syndrome is a multisystemic disorder caused by a microdeletion of the 7q11.23 region. Although familial cases with autosomal dominant inheritance have been reported, the vast majority are sporadic. Objective: To investigate the main complaints and clinical findings of patients with Williams-Beuren syndrome. Methods: A total of 757 parents of patients registered in the Brazilian Association of Williams-Beuren Syndrome (ABSW) received a questionnaire via WhatsApp from March to July 2017. Results: In total, 229 parents answered the survey. Age of diagnosis ranged from 2 days to 34 years (median: 3 years). The main clinical findings reported by the parents were abdominal colic (83.3%), failure to thrive (71.5%), feeding difficulty in the first year (68.9%), otitis (56.6%), urinary tract infections (31.9%), precocious puberty (27.1%) and scoliosis (15.9%). Cardiac defects were present in 66% of patients, and the most frequent defect was supravalvular aortic stenosis (36%). Arterial hypertension was reported in 23%. Hypercalcemia was reported in 10.5% of patients, mainly during the first year of life. Hyperacusis and hypersociability were common complaints (both present in 89%). Other behavioral and neuropsychiatric symptoms reported by the parents included attention deficit (89%), anger crises (83%), excessive fear (66%), depression (64%), anxiety (67%) and hypersexuality (33%). The most common complaints were hypersensitivity to sounds, talkative personality, emotional dependence and learning difficulties. In 98.3%, the parents denied family history. Conclusions: Williams-Beuren syndrome requires close follow-up with different medical specialties due to their variable clinical comorbidities, including language and school learning difficulties, behavioral and psychiatric problems.

RESUMO Antecedentes: A síndrome de Williams-Beauren é doença de acometimento multisistêmico causado pela microdeleção da região 7q11.23. Apesar de haver casos familiares com herança autossômica dominante, a grande maioria dos casos é esporádica. Objetivo: Investigar as principais queixas e achados clínicos da síndrome. Métodos: 757 pais de pacientes inscritos na Associação Brasileira de Síndrome de Williams-Beuren (ABSW) receberam um questionário pelo WhatsApp, entre março e julho de 2017. Resultados: 229 pais de pacientes responderam à pesquisa. A idade de diagnóstico variou de 2 dias até 34 anos (mediana: 3 anos). Os principais achados reportados pelos pais: cólicas abdominais (83,3%), deficiência ponderoestatural (71,5%), dificuldade de alimentação no primeiro ano (68,9%), otite (56,6%), infecções do trato urinário (31,9%), puberdade precoce (27,1%) e escoliose (15,9%). Cardiopatias estavam presentes em 66%, sendo que a mais frequente era a estenose pulmonar supravalvar (36%). Hipertensão arterial foi reportada em 23%. Hipercalcemia foi reportada em 10,5%, principalmente no primeiro ano de vida. Hiperacusia e hiperssociabilidade foram achados comuns (89%). Os principais achados comportamentais e psiquiátricos reportados pelos pais foram: déficit de atenção (89%), crises de raiva (83%), medo excessivo (66%), depressão (64%), ansiedade (67%) e hiperssexualidade (33%). As queixas principais referidas foram hipersensibilidade a sons, personalidade excessivamente amigável, dependência emocional e dificuldades escolares. Em 98,3% dos casos os pais negaram história familial. Conclusões: A síndrome de Williams-Beuren é requer um seguimento e manejo estritos, com diferentes especialidades médicas devido às comorbidades clínicas variadas, que incluem dificuldades de linguagem e aprendizagem escolar, além de dificuldades comportamentais e psiquiátricas.

Genetic analysis of a child with atypical Williams-Beuren syndrome presenting as supravalvular aortic stenosis / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with supravalvular aortic stenosis.@*METHODS@#The child and his parents were subjected to conventional G-banding karyotyping, array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis.@*RESULTS@#No karyotypic abnormality was detected in the child and his parents. aCGH has identified a de novo 278 kb deletion encompassing the ELN gene in 7q11.23, which overlapped with the critical region of Williams-Beuren syndrome (WBS). MLPA has confirmed above findings.@*CONCLUSION@#The proband was diagnosed with atypical WBS. Deletion of the ELN gene may predispose to supravalvular aortic stenosis in the proband.

Importance of SERCA2a on early isolated diastolic dysfunction induced by supravalvular aortic stenosis in rats

Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively. After 6 weeks, the animals were submitted to echocardiogram and functional analysis by isolated papillary muscle (IPM) in basal condition, hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and phospholamban detection. Data analysis was carried out with Student's t-test and ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection fraction. Basal condition in IPM showed similar increases in developed tension (DT) and resting tension (RT) in AoS, and hypoxia was similar between groups. After cyclopiazonic acid blockage, final DT was equally decreased and RT was similar between groups, but the speed of relaxation was decreased in the AoS group. Western-blot was uniform in all evaluations. The hypothesis was confirmed, since functional parameters regarding SERCA2a were changed in the AoS group.

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.

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.

Early Manifestation of Supravalvular Aortic and Pulmonary Artery Stenosis in a Patient with Williams Syndrome

Williams syndrome (WS) is a developmental disorder characterized by vascular abnormalities such as thickening of the vascular media layer in medium- and large-sized arteries. Supravalvular aortic stenosis (SVAS) and peripheral pulmonary artery stenosis (PPAS) are common vascular abnormalities in WS. The natural course of SVAS and PPAS is variable, and the timing of surgery or intervention is determined according to the progression of vascular stenosis. In our patient, SVAS and PPAS showed rapid concurrent progression within two weeks after birth. We report the early manifestation of SVAS and PPAS in the neonatal period and describe the surgical treatment for stenosis relief.

Multivariate Analysis for Animal Selection in Experimental Research / Análise Multivariada na Seleção de Animais em Pesquisas Experimentais

Background: Several researchers seek methods for the selection of homogeneous groups of animals in experimental studies, a fact justified because homogeneity is an indispensable prerequisite for casualization of treatments. The lack of robust methods that comply with statistical and biological principles is the reason why researchers use empirical or subjective methods, influencing their results. Objective: To develop a multivariate statistical model for the selection of a homogeneous group of animals for experimental research and to elaborate a computational package to use it. Methods: The set of echocardiographic data of 115 male Wistar rats with supravalvular aortic stenosis (AoS) was used as an example of model development. Initially, the data were standardized, and became dimensionless. Then, the variance matrix of the set was submitted to principal components analysis (PCA), aiming at reducing the parametric space and at retaining the relevant variability. That technique established a new Cartesian system into which the animals were allocated, and finally the confidence region (ellipsoid) was built for the profile of the animals’ homogeneous responses. The animals located inside the ellipsoid were considered as belonging to the homogeneous batch; those outside the ellipsoid were considered spurious. Results: The PCA established eight descriptive axes that represented the accumulated variance of the data set in 88.71%. The allocation of the animals in the new system and the construction of the confidence region revealed six spurious animals as compared to the homogeneous batch of 109 animals. Conclusion: The biometric criterion presented proved to be effective, because it considers the animal as a whole, analyzing jointly all parameters measured, in addition to having a small discard rate. .

Fundamento: Muitos pesquisadores buscam métodos para a seleção de grupos homogêneos de animais em pesquisas experimentais, fato que se justifica por ser a homogeneidade pré-requisito indispensável à casualização de tratamentos. A ausência de métodos robustos, que atendam a princípios estatísticos e biológicos, faz com que os pesquisadores utilizem métodos empíricos ou subjetivos, influenciando seus resultados. Objetivo: Desenvolver modelo estatístico multivariado para a seleção de grupo homogêneo de animais para pesquisas experimentais e elaborar pacote computacional que o operacionalize. Métodos: O conjunto de dados ecocardiográficos de 115 ratos Wistar, machos, com estenose aórtica (EAo) supravalvular foi utilizado para exemplificar o desenvolvimento do modelo. Inicialmente, os dados foram padronizados, tornando-se adimensionais. Em sequência, submeteu-se a matriz de variabilidade do conjunto à análise de componentes principais (ACP) buscando-se reduzir o espaço paramétrico e conservar a variabilidade relevante. Essa técnica estabeleceu um novo sistema cartesiano em que os animais foram alocados e, finalmente, construiu-se a região de confiança (elipsoide) para o perfil de respostas homogêneas dos animais. Os que se situaram no interior do elipsoide foram considerados pertencentes ao grupo homogêneo; caso contrário, espúrios ao grupo. Resultados: A ACP estabeleceu oito eixos descritores que representaram a variabilidade acumulada dos dados em 88,71%. A alocação dos animais no novo sistema e a construção da região de confiança revelou a presença de seis espúrios ao lote homogêneo formado por 109 animais. Conclusão: O critério biométrico proposto mostra-se eficiente, pois considera o animal como um todo, analisando conjuntamente todos os parâmetros mensurados, além de apresentar pequena frequência de descartes. .

Cleft anterior mitral leaflet with supravalvular aortic stenosis a rare association

A 20 year old female was referred to us for evaluation of effort dyspnoea of NYHA class II with feeble left common carotid, left brachial and left radial artery as compared to other sides. Detail evaluation with two dimensional [2D] transthoracic echocardiographic, 2D transesophageal echocardiography and multidetector computed tomography [MDCT] delineated Cleft AML and diffuse type of supravalvular aortic stenosis. To the best of our knowledge, no such case have been described in the literature where these anomalies co-existed in the same patient

Estenose aórtica supravalvar em adulto com anomalia de vasos da base e insuficiência aórtica / Supravalvular aortic stenosis in adult with anomalies of aortic arch vessels and aortic regurgitation

A estenose aórtica supravalvar é uma rara cardiopatia congênita, bastante incomum em adultos. Apresentamos um caso de estenose aórtica supravalvar em adulto com anomalia de vasos do arco aórtico, já com presença de insuficiência aórtica importante, tratado com êxito por meio de plastia da aorta ascendente e troca valvar aórtica.

The supravalvular aortic stenosis is a rare congenital heart defect being very uncommon in adults. We present a case of supravalvular aortic stenosis in adult associated with anomalies of the aortic arch vessels and aortic regurgitation, which was submitted to aortic valve replacement and arterioplasty of the ascending aorta with a good postoperative course.

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.

Influência do aumento energético proveniente de dieta hiperlipídica na disfunção cardíaca em ratos com estenose aórtica supravalvar: participação das cadeias pesadas de miosina e da bomba de cálcio do retículo sarcoplasmático / Influence of energetic increase from fat diet in cardiac dysfunction in rats with aortic stenosis supravalvular: participation of the heavy chains of myosin and calcium pump of sarcoplasmic reticulum

A remodelação cardíaca (RC) ocorre em resposta a determinadas agressões como, por exemplo, sobrecarga pressórica, e pode manifestar-se por alterações de tamanho, forma e função do coração. No modelo de estenose aórtica supravalvar (EAo) em ratos, estudos ecocardiográficos constataram que, 2 e 6 semanas após indução da EAo, os ratos desenvolvem hipertrofia ventricular esquerda, disfunção diastólica e melhoria da função sistólica. Após 12 semanas há disfunção sistólica e perto da 20ª semana aparecem sinais de insuficiência cardíaca. Diversos fatores poderiam contribuir para a disfunção neste modelo experimental, como modificações na expressão proteica da bomba de cálcio do retículo sarcoplasmático (SERCA2a) e das cadeias pesadas de miosina (MyHC), ambas com alta capacidade ATPásica. Na RC patológica ocorre diminuição na beta oxidação de ácidos graxos, podendo acarretar déficit energético para o músculo cardíaco hipertrofiado. O objetivo deste trabalho foi testar a hipótese de que o aumento da oferta energética, proveniente de dieta hiperlipídica, atenua a disfunção diastólica e preserva a função sistólica no modelo de EAo. Os mecanismos envolvidos na preservação ou melhoria da função estão relacionados com a diminuição na transição da isoforma V1(α) para V3(β) da MyHC e com o aumento da relação SERCA2a/PLB. Foram utilizados ratos Wistar machos, com 21 dias, separados em dois grupos: controle operado (Sham) e estenose aórtica supravalvar (EAo). Seis semanas após cirurgia, os animais foram redistribuídos em quatro grupos (n=12/grupo): tratados com dieta normolipídica (EAo-N e Sham-N) ou hiperlipídica (EAo-H e Sham-H) por 12 semanas. O perfil nutricional foi determinado pelas análises de ingestão alimentar e calórica, eficiência alimentar, peso e gordura corporal, índice de adiposidade, glicemia, triacilglicerol e ácidos graxos livres não-esterificados...

Cardiac remodeling (CR) occurs in response to some cardiac injuries, such as pressure overload, and it may be manifested as changes in size, shape and function of the heart. In the model of supravalvar aortic stenosis (SVAS), echocardiographic studies performed in our laboratory showed that, 2 and 6 weeks post SVAS induction, rats developed left ventricular hypertrophy, diastolic dysfunction and improved systolic function. After 12 weeks there is systolic dysfunction and around the 20th week signs of heart failure appear. Several factors could contribute to the dysfunction in this experimental model, such as changes in protein expression of sarcoplasmic reticulum calcium ATPase (SERCA2a) and myosin heavy chain (MyHC), both with high ATPase capacity. Pathological CR is underscored by a reduction in fatty acid beta oxidation, which may cause energy deficit to the hypertrophied cardiac muscle. The aim of this work was to test the hypothesis that increased energy supply, derived from high-fat diet, attenuates cardiac dysfunction in the SVAS model. The mechanisms involved in the attenuation of dysfunction are related to decreased V1(α) to V3(β) MyHC isoform transition and increased SERCA2a/PLB ratio. Male Wistar rats, aged 21 days, were separated into two groups: operated control (Sham) and supravalvar aortic stenosis (SVAS). Six weeks after surgery, the animals were redistributed into four groups (n=12/group): fed with normolipidic diet (Sham-N and SVAS-N) or high-fat diet (Sham-H and SVAS-H). The nutritional profile was determined by food and calorie intake, feed efficiency, weight and body fat, adiposity index, blood glucose, triacylglycerol and non-esterified free fatty acid. The CR was characterized by analyses of the cardiac structure and function by echocardiogram in the 6th and 18th week, macroscopic study, energy metabolism and SERCA2a/PLB and β/α MyHC cardiac ratios...

Detecção da microdeleção 7q11.23 por MLPA® e estudo clínico dos pacientes com síndrome de Williams-Beuren / Detection of the microdeletion 7q11.23 by MLPA® and clinical study of patients with Williams-Beuren syndrome

INTRODUÇÃO: A síndrome de Williams-Beuren (SWB) é uma doença genética causada por uma microdeleção na região 7q11.23 e caracterizada por dismorfismos faciais típicos, deficiência intelectual, comportamento hipersociável, cardiopatia congênita, principalmente a estenose aórtica supravalvar (EASV), e outras malformações variáveis. MÉTODOS: Foram avaliados 65 pacientes (40 do sexo masculino, 25 do sexo feminino), com idades entre 2 e 59 anos (mediana = 14 anos), com características clínicas sugestivas de SWB. Todos os pacientes eram filhos de pais normais. A técnica de Multiplex Ligation-dependent Probe Amplification® (MLPA®) foi usada com kit específico com sondas da região da SWB (MRC Holland). As sondas foram hibridadas ao DNA e os fragmentos ligados foram amplificados por PCR e analisados com software específico. RESULTADOS: A deleção de todas as sondas da região 7q11.23 testadas foi detectada por MLPA® em 55/65 pacientes. Um caso de deleção atípica, ou seja, menor que 1,5 Mb, foi observada em um paciente com quadro clínico parcial da síndrome. Os nove pacientes sem deleção tinham um diagnóstico clínico duvidoso da SWB. Dois pacientes tiveram MLPA® positivo para SWB embora apresentassem resultados de FISH negativos...

INTRODUCTION: Williams-Beuren syndrome (WBS) is a genetic disorder caused by a microdeletion in 7q11.23 region. It is characterized by typical facial dysmorphisms, mental retardation, hipersociable behavior, congenital heart disease, mainly supravalvular aortic stenosis (SVAS), and other variable congenital malformations. METHODS: 65 patients (40 males, 25 females), aged 2-59 years old (median = 14 years old), with clinical characteristics suggesting WBS, were evaluated. All patients had normal parents. Multiplex Ligation-dependent Probe Amplification® (MLPA®) was performed with a kit with probes in WBS region (MRC Holland). The probes were hybridized to the DNA and the ligated fragments were amplified by PCR and analyzed with specific software. RESULTS: The deletion for all tested probes in the 7q11.23 region was detected by MLPA® in 55/65 patients. One case of atypical deletion, smaller than 1.5 Mb, was observed in one patient with partial clinical picture of the syndrome. The nine patients without the deletion did not have a definitive clinical diagnosis of WBS. Two patients had positive MLPA® results even though they had negative FISH for WBS...

Puérpera com trombose de prótese mecânica e estenose supravalvar aórtica adquirida / Postpartum patient with thrombosis of mechanical prostheses and acquired supravalvular aortic stenosis

A hipercoagulabilidade sanguínea proporcionada na gravidez aumenta consideravelmente a incidência de trombose de valvas mecânicas. A estenose supravalvar aórtica adquirida é extremamente rara. Relata-se o caso de uma puérpera imediata, portadora de prótese mecânica aórtica e estenose supravalvar aórtica adquirida, submetida à cirurgia cardíaca de emergência, com instabilidade hemodinâmica grave, por meio de técnica operatória adaptada para a correção da estenose supravalvar aórtica, com evolução clínica e resultados ecocardiográficos pós-operatórios satisfatórios.

The blood hypercoagulability in pregnancy increases significantly the incidence of thrombosis of mechanical valves. Acquired supravalvular aortic stenosis is extremely rare. We report the case of an immediate postpartum patient with aortic mechanical prostheses and acquired supravalvular aortic stenosis who underwent emergency heart surgery, with severe hemodynamic instability, using adapted surgical technique for correction of supravalvular stenosis with satisfactory clinical and echocardiography results.

A clinical and molecular cytogenetic study of Filipino patients with williams syndrome

Objective. To study the clinical spectrum of Filipino patients with Williams Syndrome and to confirm the gene deletion by FISH analysis. Methods. From June 2005 to September 2008, patients who were seen at the Genetics clinic of the UP-PGH and who met the clinical criteria for Williams Syndrome were analyzed for the 7q11.23 deletion through karyotyping and FISH studies. A detailed history and a thorough dysmorphologic examination were performed. Relevant investigations included two-dimensional echocardiography, renal ultrasonography, ophthalmologic examination, developmental assessment and serum calcium determination. Result. Eight patients were included in the study. The mean age at first diagnosis was 8.5 years. All cases were sporadic. The chromosomal analysis was normal for all patients and in the FISH analysis, a 7q11.23 deletion was detected in 100% of cases. Distinctive facial features, cardiac abnormalities and developmental delay were present in all patients. The typical behavior of overfriendliness was observed in the majority of cases. Hypercalcemia was documented in only one case and no renal anomalies were detected. Conclusion. The craniofacial features were similar among patients but there is a broad spectrum of severity of clinical features in cardiovascular abnormalities, personality, behavior traits and mental capacity.

Correção cirúrgica da estenose aórtica supravalvar com modificação da técnica de Sousa / Supravalvular aortic stenosis surgical repair using modified Sousa's technique

Relato de uma paciente de sete anos apresentando progressiva intolerância ao esforço. A criança apresentava taquicardia e sopro pansistólico de maior intensidade no foco aórtico. O ecocardiograma evidenciava hipertrofia ventricular esquerda e estenose aórtica supravalvar com gradiente sistólico de 190 mmHg. A angioressonância e o cateterismo cardíaco confirmaram o diagnóstico, sugerindo estenose do óstio da artéria coronária esquerda. A correção foi realizada modificando a técnica descrita por Sousa. A evolução pósoperatória transcorreu sem intercorrências, com gradiente pós-operatório de 23 mmHg e boa mobilidade da valva aórtica.

Report of a patient with seven years old and effort intolerance progressing. The child had tachycardia, pansystolic murmur in the aortic focus. Echocardiography showed left ventricle hypertrophy and aortic narrowing at the level of sinotubular junction with sistolic gradient of 190 mmHg. Cardiac catheterization confirmed the diagnostic suggesting left coronary ostium stenosis. The surgery was performed modification the technique, described by Sousa. Immediate post-operative has presented no complications, with gradient of 23 mmHg, and good leaflets mobility.

Sudden cardiac death under anesthesia in pediatric patient with williams syndrome: A case report and review of literature.

Williams syndrome is a complex syndrome characterized by developmental abnormalities, craniofacial dysmorphic features, and cardiac anomalies. Sudden death has been described as a very common complication associated with anesthesia, surgery, and procedures in this population. Anatomical abnormalities associated with the heart pre-dispose these individuals to sudden death. In addition to a sudden and rapid downhill course, lack of response to resuscitation is another significant feature seen in these patients. The authors report a five-year-old male with Williams syndrome, hypothyroidism, and attention deficit hyperactivity disorder. He suffered an anaphylactic reaction during CT imaging with contrast. Resuscitation was unsuccessful. Previous reports regarding the anesthetic management of patients with Williams are reviewed and the potential for sudden death or peri-procedure related cardiac arrest discussed in this report. The authors also review reasons for refractoriness to defined resuscitation guidelines in this patient population.

Remodelamento cardíaco: análise seriada e índices de detecção precoce de disfunção ventricular / Cardiac remodeling: serial analysis and indexes for early detection of ventricular dysfunction / Remodelación cardiaca: análisis seriado e índices de detección precoz de disfunción ventricular

Fundamento: A estenose aórtica supravalvar (EAo) é utilizada para o estudo da remodelação cardíaca (RC) por sobrecarga pressórica. Nesse modelo, não estão claramente estabelecidos o comportamento da RC desde a fase inicial, nem os melhores parâmetros para a identificação da disfunção ventricular. OBJETIVOS: 1) Caracterizar, precoce e evolutivamente, as modificações morfofuncionais durante a RC em ratos com EAo e 2) identificar o índice mais sensível para detecção do momento do aparecimento da disfunção diastólica e sistólica do ventrículo esquerdo (VE). Métodos: Ratos Wistar foram divididos em dois grupos - controle (GC, n=13) e EAo (GEAo, n=24) - e estudados nas 3ª, 6ª, 12ª e 18ª semanas pós-cirurgia. Os corações foram analisados por meio de ecocardiograma (ECO). Resultados: Ao final do experimento, as relações do VE, do ventrículo direito e dos átrios com o peso corporal final foram aumentadas no GEAo. O ECO mostrou que o átrio esquerdo sofreu uma remodelação significativa a partir da 6ª semana. No GEAo, a porcentagem de encurtamento endocárdico apresentou queda significativa a partir da 12ª semana e a porcentagem de encurtamento mesocárdico, na 18ª semana. A relação onda E e onda A (E/A) foi superior no GC em comparação ao GEAo em todos os momentos analisados. Conclusões: O ventrículo esquerdo dos ratos com EAo, durante o processo de remodelação, apresentou hipertrofia concêntrica, disfunção diastólica precoce e melhoria da função sistólica, com posterior deterioração do desempenho. Além disso, constatou-se que os índices ecocardiográficos mais sensíveis para a detecção da disfunção diastólica e sistólica são, respectivamente, a relação E/A e a porcentagem de encurtamento endocárdico.

Background: Supravalvar aortic stenosis (SVAS) is used to study overload-induced cardiac remodeling (CR). In this model, neither CR behavior since beginning stage nor the best parameters to identify ventricular dysfunction are clearly stated. Objective: 1) Characterizing, early and evolutively, morphological and functional modifications during CR in rats with SVAS and 2) identifying the most sensitive index for detecting the moment when the diastolic and systolic dysfunction first appeared in the left ventricle (LV). Methods: Wistar Rats were divided into two groups - control (CG, n=13) and SVAS (SVASG, n=24) - and studied in post-surgical 3rd, 6th, 12th and 18th weeks. Hearts were analyzed by means of an echocardiogram (ECHO). Results: By the end of the experiment, ratios between the LV, right ventricle and atria and the final body weight were increased in the SVASG. The ECHO showed that the left atrium underwent significant remodeling from the 6th on. The percent of endocardial shortening underwent significant drop as of the 12nd week and the percent of, as of the 18th week, in the SVASG. The ratio between E- wave and A-wave (E/A) was higher in CG compared to the SVASG in all events analyzed. Conclusions: During the remodeling process, the left ventricle of rats with SVAS presented concentric hypertrophy, early diastolic dysfunction and improvement of systolic function, with posterior performance deterioration. Besides this, the study found out the most sensitive echocardiographic indexes for detecting systolic and diastolic dysfunction are, respectively, the ratio E/A and the percent of endocardial shortening.

Fundamento: La estenosis aórtica supravalvular (EAo) se utiliza para el estudio de la remodelación cardiaca (RC) por sobrecarga de presión. En este modelo, no están claramente establecidos el comportamiento del RC desde la fase inicial, ni los mejores parámetros para la identificación de la disfunción ventricular. OBJETIVO: 1) Caracterizar, precoz y evolutivamente, las modificaciones morfofuncionales durante el RC en ratones con EAo, y 2) identificar el índice más sensible para detección del momento de la aparición de la disfunción diastólica y sistólica del ventrículo izquierdo (VI). Métodos: Ratones Wistar se dividieron en dos grupos - control (GC, n=13) y EAo (GEAo, n=24) - y estudiados en las 3ª, 6ª, 12ª y 18ª semanas post cirugía. Los corazones se analizaron por medio de ecocardiograma (ECO). Resultados: Al final del experimento, las relaciones del VI, del ventrículo derecho y de los atrios con el peso corporal final fueron aumentadas en el GEAo. El ECO mostró que el atrio izquierdo sufrió una remodelación significativa a partir de la 6ª semana. En el GEAo, el porcentaje de acortamiento endocárdico presentó disminución significativa a partir de la 12ª semana y el porcentaje de acortamiento mesocárdico, en la 18ª semana. La relación onda E y onda A (E/A) fue superior en el GC en comparación al GEAo en todos los momentos analizados. Conclusión: El ventrículo izquierdo de los ratones con EAo, durante el proceso de remodelación, presentó hipertrofia concéntrica, disfunción diastólica precoz y mejora de la función sistólica, con posterior deterioro del desempeño. Además de ello, se constató que los índices ecocardiográficos más sensibles para la detección de la disfunción diastólica y sistólica son, respectivamente, la relación E/A y el porcentaje de acortamiento endocárdico.

Mitral Valve Repair for Congenital Mitral Regurgitation in Children / 대한흉부외과학회지

BACKGROUND: Surgery for mitral valve disease in children carries both technical and clinical difficulties that are due to both the wide spectrum of morphologic abnormalities and the high incidence of associated cardiac anomalies. The purpose of this study is to assess the outcome of mitral valve surgery for treating congenital mitral regurgitation in children. MATERIAL AND METHOD: From 1997 to 2007, 22 children (mean age: 5.4 years) who had congenital mitral regurgitation underwent mitral valve repair. The median age of the patients was 5.4 years old and four patients (18%) were under 12 months of age. 15 patients (68%) had cardiac anomalies. There were 13 cases of ventricular septal defect, 1 case of atrial septal defect and 1 case of supravalvar aortic stenosis. The grade of the preoperative mitral valve regurgitation was II in 4 patients, III in 15 patients and IV in 3. The regurgitation was due to leaflet prolapse in 12 patients, annular dilatation in 4 patients and restrictive leaflet motion in 5 patients. The preoperative MV Z-value and the regurgitation grade were compared with those obtained at follow-up. RESULT: MV repair was possible in all the patients. 19 patients required reduction annuloplasty and 18 patients required valvuloplasty that included shortening of the chordae, papillary muscle splitting, artificial chordae insertion and cleft closure. There were no early or late deaths. The mitral valve regurgitation after surgery was improved in all patients (absent=10, grade I=5, II=5, III=2). MV repair resulted in reduction of the mitral valve Z-value (2.2+/-.1 vs. 0.7+/-.3, respectively, p<0.01). During the mid-term follow-up period of 3.68 years, reoperation was done in three patients (one with repair and two with replacement) and three patients showed mild progression of their mitral regurgitation. CONCLUSION: Our experience indicates that mitral valve repair in children with congenital mitral valve regurgitation is an effective and reliable surgical method with a low reoperation rate. A good postoperative outcome can be obtained by preoperatively recognizing the intrinsic mitral valve pathophysiology detected on echocardiography and with the well-designed, aggressive application of the various reconstruction techniques.