Cardiovascular findings in Williams-Beuren Syndrome: Experience of a single center with 127 cases.

Williams-Beuren syndrome (WBS) is a rare, microdeletion syndrome characterized by facial dysmorphisms, intellectual disability, a friendly personality, cardiovascular and other abnormalities. Cardiovascular defects (CVD) are among the most prevalent characteristics in WBS, being supravalvular aortic stenosis (SVAS) the most frequent, followed by peripheral pulmonary stenosis (PPS). A comprehensive retrospective review of medical records of 127 patients with molecular diagnosis of WBS, in a period of 20 years, was done to evaluate the incidence, the natural history of cardiovascular disease, and the need for surgical intervention, including heart transplantation (HT). A total of 94/127 patients presented with CVD. Of these 94 patients, 50% presented with SVAS and 22.3% needed heart surgery and/or cardiac catheterization including one that required HT due to severe SVAS-related heart failure at 19 years of age. The patient died in the postoperative period due to infectious complications. Cardiovascular problems are the major cause of sudden death in patients with WBS, who have a significantly higher mortality risk associated with surgical interventions. There is a higher risk for anesthesia-related adverse events and for major adverse cardiac events following surgery. End-stage heart failure due to myocardial ischemia has been described in WBS patients and it is important to consider that HT can become their only viable option. To our knowledge, the case mentioned here is the first HT reported in an adolescent with WBS. HT can be a viable therapeutic option in WBS patients with adequate evaluation, planning, and a multidisciplinary team to provide the required perioperative care and follow-up.

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

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

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.

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

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

[Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature]. / Uso do eculizumab na síndrome hemolítica urêmica atípica: relato de caso e revisão da literatura.

SHU atypical (aHUS), that is, not associated with Escherichia coli Shiga toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS), and can occur at any age and may be sporadic or familial. The prognosis in these cases is reserved, with high mortality and morbidity in the acute phase of the disease, and about 50% of cases can develop chronic kidney disease. The increased knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway of complement), was accompanied by the appearance of a drug, eculizumab, which acts as an inhibitor of membrane attack complex. Our goal is to report a case of infant with aHUS with excellent clinical and laboratory response with the use of eculizumab. 14 month old infant, previously healthy, male, presented anemia and thrombocytopenia at 12 months of age. He was treated with corticosteroids and forwarded to our service for high blood pressure. However, the scans showed nephrotic proteinuria with renal involvement and hypoalbuminemia with direct Coombs negative. He developed anemia, thrombocytopenia, worsening of renal function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA). On the non-hemolytic anemia, thrombocytopenia and acute renal failure with histological substrate MAT, was diagnosed of aHUS. The patient received eculizumab excellent clinical and laboratory response. This case shows the importance of early diagnosis and treatment of the aHUS. Eculizumab is effective and keeps long-term remission, avoiding invasive measures such as plasmapheresis, which resolves only part of the picture.

Uso do eculizumab na síndrome hemolítica urêmica atípica: relato de caso e revisão da literatura / Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature

Síndrome Hemolítico Urêmica atípica (SHUa), isto é, não associada à Escherichia coli, produtora de Shiga toxina, é vista em 5% a 10% dos casos de Síndrome Hemolítico Urêmica (SHU), podendo ocorrer em qualquer idade e ser esporádica ou familiar. O prognóstico nestes casos é reservado, com alta mortalidade e morbidade na fase aguda da doença, e cerca de 50% dos casos podem evoluir para doença renal crônica terminal. O aumento do conhecimento da patôgenese da SHUa (hiperativação da via alternativa do complemento) foi acompanhado pelo surgimento de uma droga, eculizumab, a qual age como inibidor da via final do complemento. Nosso objetivo é relatar um caso de lactente com SHUa que apresentou excelente resposta clínica e laboratorial com o uso de eculizumab. Lactente, 14 meses de idade, sexo masculino, previamente hígido, apresentou quadro de anemia e plaquetopenia aos 12 meses de idade. Foi tratado com corticoterapia e encaminhado ao nosso serviço por hipertensão arterial. Entretanto, os exames demonstraram acometimento renal com proteinúria nefrótica e hipoalbuminemia, com Coombs direto negativo. Evoluiu com anemia, plaquetopenia, piora de função renal e hipertensão. Realizada biópsia renal que mostrou microangiopatia trombótica (MAT). Diante do quadro de anemia não hemolítica, plaquetopenia e insuficiência renal aguda com substrato histológico de MAT, foi feito diagnóstico de SHUa. O paciente recebeu eculizumab, com excelente resposta clínico-laboratorial. Este caso denota a importância de diagnóstico e tratamento precoces nesta entidade grave que é a SHUa. Eculizumab é eficaz e mantém remissão a longo prazo, evitando medidas invasivas como a plasmaferese, a qual resolve apenas parcialmente o quadro.

SHU atypical (aHUS), that is, not associated with Escherichia coli Shiga toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS), and can occur at any age and may be sporadic or familial. The prognosis in these cases is reserved, with high mortality and morbidity in the acute phase of the disease, and about 50% of cases can develop chronic kidney disease. The increased knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway of complement), was accompanied by the appearance of a drug, eculizumab, which acts as an inhibitor of membrane attack complex. Our goal is to report a case of infant with aHUS with excellent clinical and laboratory response with the use of eculizumab. 14 month old infant, previously healthy, male, presented anemia and thrombocytopenia at 12 months of age. He was treated with corticosteroids and forwarded to our service for high blood pressure. However, the scans showed nephrotic proteinuria with renal involvement and hypoalbuminemia with direct Coombs negative. He developed anemia, thrombocytopenia, worsening of renal function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA). On the non-hemolytic anemia, thrombocytopenia and acute renal failure with histological substrate MAT, was diagnosed of aHUS. The patient received eculizumab excellent clinical and laboratory response. This case shows the importance of early diagnosis and treatment of the aHUS. Eculizumab is effective and keeps long-term remission, avoiding invasive measures such as plasmapheresis, which resolves only part of the picture.

Comparação das medidas de pressão arterial no consultório, no domicílio e pela monitorização ambulatorial da pressão arterial (MAPA) em crianças com hipertensão arterial / Comparison of blood pressure measurement in the office, at home and ambulatory blood pressure (ABP) in children with arterial hypertension

O diagnóstico e acompanhamento da hipertensão arterial (HA) no paciente pediátrico dependem da acurácia e da representatividade da medida da pressão arterial (PA). A monitorização ambulatorial da pressão arterial (MAPA), apesar de suas vantagens em relação à medida casual, apresenta custo elevado e pode trazer desconforto ao paciente. A medida residencial da pressão arterial (MRPA), apesar de pouco estudada na criança, apresenta-se como um alternativo potencial à MAPA. Os objetivos deste estudo foram comparar as medidas da PA aferidas no consultório, na MRPA, na Liga de Hipertensão e pela MAPA avaliando o efeito do ambiente/observador e determinando a freqüência de valores compatíveis com HA nessas 4 situações. Este estudo foi transversal,prospectivo e foram incluídos pacientes com HA e PA controlada ou não no consultório. Foram analisadas as médias das pressões arteriais sistólicas e diastólicas. A MRPA foi realizada com aparelho OMRON HEM 705 CP por 14 dias, em dois períodos (manhã ou tarde e noite). Na véspera do início da MRPA, o paciente compareceu à Liga de Hipertensão do HC-FMUSP para colocação do equipamento da MAPA (SPACELABS 90207). Foram analisados os dados de 40 pacientes (14 meninas e 26 meninos), idade média 12,1±3,6 anos. Não houve diferença estatística entre as médias das pressões sistólicas (ANOVA p=0,3100) e diastólicas (ANOVA p=0,7700) no consultório com as médias diurnas da MRPA e nem com as médias sistólicas (ANOVA p=0,8240) e diastólicas(ANOVA p=0,1530) do período noturno da MRPA. As médias das pressões sistólicas e diastólicas da Liga e da MAPA foram maiores do que as médias do consultório e da MRPA (p<0,001), porém não houve diferença estatística entre as médias sistólicas e diastólicas da Liga com a MAPA (p=0,077) e (p=0,962) respectivamente. As médias das pressões diastólicas da MRPA foram menores do que as médias do consultório (p=0,001). Em relação à freqüência de pacientes com PA não controlada, esta foi maior na...

The diagnosis and monitoring of hypertension in pediatric patients depend on the accuracy and reproducibility of blood pressure (BP) measurement. Ambulatory blood pressure monitoring (ABPM), despite its advantages over office BP, is costly and can cause discomfort to the patient. The blood pressure measured at home (HBP), although poorly studied in children, represents a potential alternative to ABPM. The objectives of this study were to compare BP measurement in four clinical conditions: office BP , casual BP measured at Liga de Hipertensão, HBP and ABPM, evaluate the effect of environment / observer and to determine the frequency of BP values compatible with the diagnosis of hypertension. This study was cross-sectional and prospective and included patients with arterial hypertension with/without properly controlled BP in the office. The means of systolic and diastolic BP were analyzed in the 4 clinical conditions. HBP was measured for 14 days using a validated fully automatic Omron HEM 705 CP device. ABPM was measured with SpaceLabs 90207 non-invasive portable oscilometric device. We analyzed data from 40 patients (14 girls and 26 boys), mean age 12.1 ± 3.6 (SD) years. There was no difference between systolic (ANOVA p = 0.3100) and diastolic (ANOVA p= 0.7700) BP in the office and daytime HBP nor with nightime systolic HBP ( ANOVA p = 0.8240) and diastolic HBP(ANOVA p = 0.1530). The average systolic and diastolic BP at the Liga de Hipertensão and ABPM were higher than office and HB P (p <0001), but there was no difference in the average systolic (p= 0.077) and diastolic (p = 0.962) BP between Liga and ABPM. The diastolic HBP was lower than office diastolic BP (p = 0001). The frequency of BP values compatible with hipertension was higher at the Liga de Hipertensão (Mc Nemar p <0005), while comparisons between officedaytime HBP, office- daytime ABPM and daytime HBP-ABPM were not significant (Mc Nemar p> 0.05). The BP measurements during nightime ABPM...

[Evaluation of the Omron 705-CP blood pressure measuring device for use in adolescents and young adults]. / Avaliação do monitor de medida de pressão arterial OMRON 705-CP para uso em adolescentes e adultos jovens.

OBJECTIVE: To assess the Omron 705-CP monitor for measuring blood pressure in adolescents and young adults. METHODS: According to the protocols of the British Hypertension Society and the Association for the Advancement of Medical Instrumentation, we performed validation of the device in 60 adolescents. The Omron monitor was connected in Y to a mercury column. Four consecutive and simultaneous measurements were taken with the mercury column sphygmomanometer and the test device, were independently analyzed, and the mean differences between the blood pressure measurements and the standard deviations of those differences were calculated. The results were analyzed according to the grading system of the protocol used. RESULTS: Two hundred and forty measurements were evaluated. The mean age of the patients was 16.3 years. When the measurement performed with the mercury column sphygmomanometer was compared with that taken with the device, a difference < or =15 mmHg was observed in 97.9% of the systolic and 98.8% of the diastolic blood pressure measurements; a difference < or =10 mmHg was observed in 86.3% of the systolic and 90.4% of the diastolic blood pressure measurements, which was classified as grade A; a difference < or =5 mmHg was observed in 59.1% of the systolic and 67% of the diastolic blood pressure measurements, and was classified as grade A/B. The mean difference and the standard deviation of that difference for the systolic blood pressure was 2.91+/-6.42 mmHg, and, for the diastolic blood pressure, it was 1.16+/-5.79 mmHg. CONCLUSION: The Omron 705-CP monitor proved to be useful for measuring blood pressure in adolescents according to the protocol used.

Avaliação do monitor de medida de pressão arterial 0mron 705-CP para uso em adolescentes e adultos jovens / Evaluation of the Omron 705-CP blood pressure measuring device for use in adolescents and young adults

OBJETIVO: Avaliar o monitor OMRON 705-CP de medida de pressão arterial em adolescentes e adultos jovens. MÉTODOS: De acordo com o protocolo da British Hypertension Society e da Association for the Advancement of Medical Instrumentation, realizamos a validação do aparelho em 60 adolescentes. O monitor foi conectado em Y com a coluna de mercúrio e foram realizadas 4 medidas consecutivas e simultâneas, analisadas as independentes e calculadas as diferenças médias entre as pressões e o desvio padrão dessas diferenças. Os resultados foram analisados de acordo com o sistema de grau do protocolo utilizado. RESULTADOS: Foram avaliadas 240 medidas. A idade média dos pacientes foi 16,3 anos. Quando comparada a medida realizada pela coluna de mercúrio com o aparelho houve uma diferença < 15 mmHg em 97,9 por cento das medidas sistólicas e 98,8 por cento das diastólicas; uma diferença < 10 mmHg em 86,3 por cento das medidas sistólicas e 90,4 por cento das diastólicas, classificada como grau A; uma diferença < 5 mmHg em 59,1 por cento das medidas sistólicas e 67 por cento das medidas diastólicas, considerada pela classificação entre A/B. A diferença média e o desvio padrão dessa diferença na pressão sistólica foi de 2,91±6,42 mmHg e para a diastólica de 1,16±5,79 mmHg. CONCLUSAO: O monitor OMRON 705-CP mostrou-se válido para medidas de pressão arterial de adolescentes segundo o protocolo empregado.

Vacina contra hepatite B em crianças com insuficiência renal crônica sob tratamento conservador / Hepatitis B vaccine in children with chronic kidney failure in conservative treatment

A vacina contra hepatite B é recomendada em pacientes com insuficiência renal crônica (IRC). Controvérsias existem acerca da melhor vacina, do melhor esquema vacinal e do período da vacinaçao, principalmente em crianças. Empregamos uma vacina recombinante contra hepatite B (Engerix Bâ, Smith Kline Biologicals), via intramuscular, no esquema #0, #1 e #6 meses, doses simples em 25 crianças (Grupo I) e doses duplas em 22 (Grupo II), todas em fase de tratamento conservador. Avaliamos a resposta pelos níveis de anticorpos anti-HBs após 1 mês da terceira dose (títulos protetores acima de 100 mUI/ml). Os pacientes do Grupo I respondenram com eficácia em 64 por cento dos casos e os do Grupo II em 86 por cento. Reforço vacinal com dose dupla foi administrado quando os títulos foram negativos ou nao protetores. O reforço produziu títulos protetores de anti-HBs em 57 por cento dos casos no Grupo I e em 100 por cento dos casos no Grupo II. O seguimento longitudinal, ainda que restrito, mostrou que os títulos de Ac anti-HBs permanecem protetores por mais tempo nas crianças do Grupo II do que nas do Grupo I. Nossos dados sugerem que crianças com IRC sob tratamento conservador devam receber a vacina recombinante (Engerix Bâ) contra hepatite B, em doses duplas no esquema habitual. A avaliaçao da resposta vacinal deve ser realizada 1 mês após a terceira dose da vacina. A manutençao de títulos protetores de anti-HBs deve ser verificada semenstralmente.

Síndrome hemolítico-urêmica atípica an criança / Atypical hemolytic-uremia syndrome in children

A Síndrome Hemolítico-Urêmica (SHU) apresenta-se como um grupo heterogêneo de doenças caracterizadas por anemia hemolítica microangiopática, plaquetopenia e insuficiência renal aguda. A lesäo histopatológica típica é a microangiopatia trombótica. A SHU hereditária ou familiar é rara e apresenta um prognóstico pior quando comparada à forma clássica ou epidêmica. Os autores relatam o caso de uma criança que apresentou o quadro clínico e histopatológico de SHU e que apresentava nos antecedentes familiares paternos, 4 adultos de 2 geraçöes com quadro de hipertensäo arterial grave, associada a gestaçäo em 2 casos, com evoluçäo para insuficiência renal. Com base nos dados clínicos e histopatológicos e através do heredograma desta família, os autores sugerem que neste caso o fator determinante da SHU possa ter sido devido a um gene autossômico dominante.