Abstract Objective: To develop growth charts for weight-for-age, height-for-age, and body mass index (BMI)-for-age for both genders aged 2 to 18 years for Brazilian patients with Williams-Beuren Syndrome (WBS). Methods: This is a multicenter, retrospective, and longitudinal study, data were collected from the medical records of boys and girls with a confirmed diagnosis of WBS in three large university centers in the state of Sao Paulo, Brazil. Growth charts stratified by gender and age in years were developed using LMSchartmaker Pro software. The LMS (Lambda Mu Sigma) method was used to model the charts. The quality of the settings was checked by worm plots. Results: The first Brazilian growth charts for weight-for-age, height-for-age, and BMI-for-age stratified by gender were constructed for WBS patients aged 2 to 18 years. Conclusion: The growth charts developed in this study can help to guide family members and to improve the health care offered by health professionals. Objective weightforage, weightforage weight age, weight-for-age heightforage, heightforage height height-for-age BMIforage BMI 1 WilliamsBeuren Williams Beuren WBS. . (WBS) Methods multicenter retrospective Paulo Brazil software Lambda Sigma plots Results Conclusion professionals (WBS

Abstract Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines. alphaNacetylglucosaminidase, alphaNacetylglucosaminidase alpha N acetylglucosaminidase, acetylglucosaminidase alpha-N-acetylglucosaminidase sulphate features 1 Brazil 72 7 2 7. identified 23 3 2- aggressiveness four decade walk Furthermore progresses 50 organomegaly problems systems guidelines 5

Abstract Background Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. Objective To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. Methods Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. Results 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). Study limitations Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). Conclusion Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients. (EB blistering Brazil biopsy recently (WES samples biopsies 6 classified , (DEB) EBS, EBS (EBS) JEB. JEB . (JEB) 1060 10 10/6 16% 16 (16% COLA COL A COL7A KRT PLEC 5 62%, 62 62% (62%) 22%, 22 22% (22%) 15%. 15% (15%) disease purposes limited only DEB) bias Also option mostly father. father father) 1/ (DEB (EBS (JEB 106 10/ (16 (62% 2 (22% (15% (1 (62 (22 (15 ( (6 (2

ABSTRACT Trisomy 13, known as Patau syndrome, is a common aneuploidy with a well-known clinical phenotype. This case report describes a trisomy 13 patient with unusual autopsy findings, including features resembling the Beckwith-Wiedemann Spectrum. Due to abnormalities of gestational ultrasounds, a prenatal karyotype of amniotic fluid cells was performed, which resulted in 47, XY+13. Autopsy microscopy studies identified leptomeningeal glioneuronal heterotopia, which was not described as belonging to Patau syndrome. Other atypical findings were diffuse hyperplasia of pancreatic islets of Langerhans and adrenals enlargement with marked adrenocortical cytomegaly, characteristically seen in the Beckwith-Wiedemann Spectrum. Molecular genetic tests were not performed for the Beckwith-Wiedemann Spectrum. Still, due to the rarity of both disorders, this report may support the evidence that trisomy 13 can affect tissue organization and lead to unusual histopathologic features resembling classic overgrowth disorders. syndrome wellknown well phenotype 1 BeckwithWiedemann Beckwith Wiedemann Spectrum ultrasounds 47 XY13 XY XY+13 heterotopia cytomegaly Still disorders 4 XY1 XY+1 XY+

RESUMO Objetivo: descrever o perfil audiológico de pacientes com Síndrome de Cornelia de Lange (SCdL), por meio de uma revisão integrativa da literatura. Métodos: após formulação da pergunta, realizou-se uma busca em seis bases de dados (Embase, ISI of Knowledge, Lilacs, Medline/PubMed, Scielo e Scopus), e fontes de informação (Google Acadêmico, OpenGrey e Proquest), com os descritores: audiologia, perda auditiva, surdez, transtornos da audição e Síndrome de Cornelia de Lange. Esta revisão foi cadastrada no Próspero, sob número CRD42020191481. Foram considerados para análise, estudos nacionais e internacionais, utilizando o direcionamento do acrônimo PECO. Para análise do risco de viés dos estudos, utilizou-se os protocolos do Instituto Joanna Briggs. Após isso, os estudos foram descritos e analisados. Resultados: dos 1.080 artigos encontrados, 12 atenderam aos critérios de inclusão. Nos resultados audiológicos, constatou-se que indivíduos com SCdL podem apresentar perda auditiva, sendo que o comprometimento pela perda auditiva condutiva foi o mais frequente, correspondendo a 49,20% dos indivíduos com SCdL avaliados, seguido pela perda auditiva neurossensorial (13,49%). O grau de perda auditiva variou de leve à profundo. Conclusão: indivíduos com SCdL frequentemente apresentam perda auditiva, decorrente principalmente de alterações de orelha média, com graus variando de leve a profundo.

ABSTRACT Purpose: to describe the audiological profile of patients with Cornelia de Lange syndrome (CdLS) in an integrative review of the literature. Methods: after developing the research question, articles were searched in six databases (EMBASE, ISI of Knowledge, LILACS, MEDLINE/PubMed, SciELO, and Scopus) and in sources of information (Google Scholar, OpenGrey, and ProQuest), with the following descriptors: audiology, hearing loss, deafness, hearing disorders, and Cornelia de Lange syndrome. This review was registered in Prospero under number CRD42020191481. National and international studies were considered for analysis, using the PECO acronym. The risk of bias in the studies was analyzed with Joanna Briggs Institute protocols. Then, the studies were described and analyzed. Results: of the 1,080 articles found, 12 met the inclusion criteria. Audiological results showed that individuals with CdLS can have hearing loss - conductive hearing losses were the most frequent impairments, corresponding to 49.20% of individuals with CdLS assessed, followed by sensorineural hearing losses (13.49%). The degrees of hearing loss ranged from mild to profound. Conclusion: individuals presented with CdLS often have hearing loss, mainly due to middle ear changes, with degrees ranging from mild to profound.

Abstract Background: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2- Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease. Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure. Nevertheless, subsequent to his tragic death, 16 affected male relatives were detected after biochemical tests identifying the low or absent activity of the IDS enzyme and confirmed by molecular analysis of the IDS gene. Following diagnosis, different options of treatment were chosen: 6 patients started ERT with Elaprase® (Idursulfase) soon after, while the other 10 remained without ERT. Eventually, 4 patients in the latter group began ERT with Hunterase® (Idursulfase Beta). None presented adverse effects to either form of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within the same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients were alive with an independent lifestyle. Conclusion: Here, the authors report the variable progress of the disease with and without ERT in a large Brazilian family with a slowly progressive form of MPS II, harboring the same missense variant in the IDS gene.

RESUMO Objetivo avaliar o perfil audiológico e a funcionalidade coclear em indivíduos com SW. Método estudo com 39 indivíduos, sendo 22 indivíduos com SW com idade entre 7 e 17 anos, sendo 15 do sexo masculino e 7 do sexo feminino e 17 indivíduos com desenvolvimento típico e normo-ouvintes. Todos os indivíduos foram avaliados por meio da audiometria tonal limiar, medidas de imitância acústica e análise das Emissões Otoacústicas Transientes (EOAT). Foi avaliado o perfil audiológico dos indivíduos com SW, e também foram comparadas as respostas das EOAT entre os indivíduos com SW sem perda auditiva e indivíduos controles. Resultados perda auditiva foi observada em 50% dos pacientes, sendo 78,95% neurossensorial e 21,05% mista. Esta perda foi predominantemente de grau leve a moderado, acometendo principalmente as frequências a partir de 3 kHz. Quanto às EOAT, observou-se maior incidência de ausência e de respostas de menor amplitude em indivíduos com SW. Conclusão indivíduos com SW apresentam disfunção das células ciliadas, principalmente da região basal da cóclea. Assim, a análise das EOAT é um recurso clínico importante a ser considerada na avaliação audiológica de rotina.

ABSTRACT Purpose to evaluate cochlear functionality in Williams syndrome (WS) individuals. Methods a study with 39 individuals, being 22 with WS aged between 7 and 17 years, 15 male and 7 female, and 17 individuals with typical development and normal hearing. All individuals were evaluated using pure tone audiometry, acoustic immittance measurements, and Transient Evoked Otoacoustic Emissions (TEOAE). The audiological profile in individuals with WS was analyzed, and TEOAE responses were compared between WS individuals without hearing loss and typical developmental individuals. Results The hearing loss was observed in 50% of patients, being 78.95% sensorineural and 21.05% mixed. This hearing loss was predominantly mild to moderate, affecting mainly frequencies above 3 kHz. As for TEOAE, there was a higher incidence of absence and lower amplitude responses in individuals with WS. Conclusion WS individuals have hair cell dysfunction, mainly in the basal region of the cochlea. Thus, TEOAE analysis is an important clinical resource to be considered in the routine audiological evaluation.

Abstract Objectives Copy Number Variations (CNVs) in the human genome account for common populational variations but can also be responsible for genetic syndromes depending on the affected region. Although a deletion in 5p is responsible for a syndrome with highly recognizable phenotypical features, other chromosomal abnormalities might overlap phenotypes, especially considering that most studies in 5p use traditional cytogenetic techniques and not molecular techniques. Methods The authors have investigated 29 patients with clinical suspicion of 5p- syndrome using Chromosomal Microarray (CMA), and have gathered information on previous tests, clinical signs, symptoms, and development of the patients. Results The results showed 23 pure terminal deletions, one interstitial deletion, one deletion followed by a 3 Mb duplication in 5p, three cases of 5p deletion concomitant to duplications larger than 20 Mb in chromosomes 2, 9, and 18, and one 5p deletion with a chromosome Y deletion. CMA showed relevant CNVs not typically associated with 5p- that may have contributed to the final phenotype in these patients. Conclusions The authors have identified three novel rearrangements between chromosomes 5 and 2 (Patient 27), 5 and 18 (Patient 11), and 5 and Y (Patient 22), with breakpoints and overlapped phenotypes that were not previously described. The authors also highlight the need for further molecular investigation using CMA, in different chromosomes beyond chromosome 5 (since those cases did not show only the typical deletion expected for the 5p- syndrome) to explain discordant chromosomal features and overlapped phenotypes to unravel the cause of the syndrome in atypical cases. HIGHLIGHTS The authors The authors have described three novel rearrangements between chromosomes 5 and 2, 5 and 18, and 5 and Y with chromosomal breakpoints and overlapped phenotypes that were not previously described. One of the main atypical features for 5p- syndrome that the authors report was the presence of seizures that was found in the three patients with rearrangements between different chromosomes and in a patient with a deletion followed by duplication in 5p. The authors suggest physicians conduct further molecular investigation in the presence of atypical clinical features for patients with 5p- syndrome suspicion.

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.

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.

Abstract Next-generation sequencing (NGS) has altered clinical genetic testing by widening the access to molecular diagnosis of genetically determined rare diseases. However, physicians may face difficulties selecting the best diagnostic approach. Our goal is to estimate the rate of possible molecular diagnoses missed by different targeted gene panels using data from a cohort of patients with rare genetic diseases diagnosed with exome sequencing (ES). For this purpose, we simulated a comparison between different targeted gene panels and ES: the list of genes harboring clinically relevant variants from 158 patients was used to estimate the theoretical rate of diagnoses missed by NGS panels from 53 different NGS panels from eight different laboratories. Panels presented a mean rate of missed diagnoses of 64% (range 14%-100%) compared to ES, representing an average predicted sensitivity of 36%. Metabolic abnormalities represented the group with highest mean of missed diagnoses (86%), while seizure represented the group with lowest mean (46%). Focused gene panels are restricted in covering select sets of genes implicated in specific diseases and they may miss molecular diagnoses of rare diseases compared to ES. However, their role in genetic diagnosis remains important especially for well-known genetic diseases with established genetic locus heterogeneity.

Resumo A Síndrome da Deleção 22q11.2 (SD22q11.2), microdeleção cromossômica mais frequente em humanos, é associada a um fenótipo neurocognitivo muito heterogêneo. Uma das principais características do espectro da síndrome é a variabilidade intelectual, que abrange de desempenho médio a deficiência intelectual, bem como discrepâncias entre Quociente de Inteligência Verbal e de Quociente de Inteligência de Execução, com maior prejuízo nas tarefas não verbais. O presente estudo teve por objetivo investigar aspectos do desempenho intelectual de uma amostra brasileira de 21 crianças e adolescentes diagnosticados com SD22q11.2, com base nos indicadores da Wechsler Intelligence Scale for Children – 4th edition. As amostras foram analisadas considerando diferenças entre os índices. Os resultados revelaram predomínio de Quociente de Inteligência Total na faixa limítrofe, entre 42 e 104, assim como discrepância significativa entre os índices de compreensão verbal e organização perceptual em 42% da amostra. No que concerne ao desempenho nos subtestes de forma isolada, um melhor resultado foi verificado em semelhanças, ao passo que cubos, raciocínio matricial, dígitos e sequência de números e letras foram os mais desafiadores. Esses achados indicam que uma avaliação abrangente de aspectos do desempenho intelectual contemplando as diversas medidas da Escala Wechsler de Inteligência pode contribuir para uma compreensão mais ampla do fenótipo neurocognitivo associado à SD22q11.2.

Abstract The 22q11.2 Deletion Syndrome (22q11.2DS), the most common human chromosome microdeletion syndrome, is associated with a very heterogeneous neurocognitive phenotype. One of the main characteristics of the syndrome spectrum is the intellectual variability, which encompasses average performance and intellectual disability and discrepancies between Verbal Intelligence Quotient and Performance Verbal Intelligence Quotient, with greater impairment in nonverbal tasks. The present study aimed at investigating the intellectual performance aspects of a 21children and adolescents sample from Brazil who had been diagnosed with 22q11.2DS, based on the Wechsler Intelligence Scale for Children - 4th edition. The samples were reviewed considering the differences between indices. The results revealed an Full Scale Intelligence Quotient predominant in the borderline range (42 to 104) and a significant discrepancy between the indices of Verbal Comprehension and Perceptual Reasoning in 42% of the sample. With regard to the performance in the subtests alone, a better performance was found in Similarities, whereas block design, matrix reasoning, digit span and letter-number sequencing subtests were the most challenging. These findings indicate that a comprehensive assessment of intellectual performance aspects covering the different measures of the Wechsler Intelligence Scale may contribute to a broader understanding of the neurocognitive phenotype associated with 22q11.2DS.

RESUMO Objetivo: descrever as características audiológicas de pacientes com Mucopolissacaridose. Métodos: após formular a pergunta de pesquisa, foram consideradas três bases de dados (Science Direct, Biblioteca Virtual em Saúde e Web of Science), sendo utilizados os seguintes descritores: mucopolissacaridoses, perda auditiva, audiologia. Foram incluídos artigos originais e completos, que apresentavam dados de avaliação audiológica em pacientes com mucopolissacaridose. Cada estudo foi classificado de acordo com o grau de recomendação e o nível de evidência científica, baseado nos critérios estabelecidos pela Oxford Centre for Evidence-based Medicine, e foram analisados os resultados obtidos nas avaliações. Resultados: dentre os 499 artigos encontrados, oito contemplaram os critérios de inclusão. A audiometria tonal e a timpanometria foram realizadas em todos os estudos. A incidência de perda auditiva em pacientes com MPS variou entre 54% a 100% dos casos, sendo que as perdas auditivas condutivas corresponderam à 30% e 58,33%, as perdas auditivas mistas corresponderam à 28,5% e 66,66% e as perdas auditivas neurossensoriais corresponderam à menos de 14%. Nenhum dos estudos descreveu as respostas das emissões otoacústicas e dos potenciais evocados auditivos. Conclusão: a prevalência de perda auditiva entre indivíduos com MPS é superior à 54% dos casos, sendo esta predominantemente condutiva e mista.

ABSTRACT Purpose: to describe the audiological characteristics of patients with mucopolysaccharidosis. Methods: after formulating the research question, three databases were considered for the search (Science Direct, Virtual Health Library and Web of Science); the following descriptors were used: mucopolysaccharidoses, hearing loss, and audiology. Articles were included that were original and complete, presenting audiological evaluation data in patients with mucopolysaccharidosis. Each study was classified according to the degree of recommendation and the level of scientific evidence, based on the criteria established by the Oxford Center for Evidence-based Medicine, and the results obtained from the evaluations were analyzed. Results: of the 499 articles found, eight met the inclusion criteria. Pure tone audiometry and tympanometry were performed in all studies. The incidence of hearing loss in patients with MPS ranged from 54% to 100% of the cases, with conductive hearing loss corresponding to 30% and 58.33%, mixed hearing loss corresponding to 28.5% and 66.66% and sensorineural hearing loss corresponding to less than 14%. None of the studies described the responses of otoacoustic emissions and auditory evoked potentials. Conclusion: the prevalence of hearing loss among individuals with MPS is higher than 54% of the cases, of which conductive and mixed are predominant.

Abstract Mucopolysaccharidoses (MPS) constitute a heterogeneous group of rare genetic disorders caused by enzymatic deficiencies that lead to the accumulation of glycosaminoglycans (GAGs). Clinical observations suggest a health-related impairment in quality of life in patients with MPS. Professionals with extensive experience in the care of patients with inborn errors of metabolism, such as MPS, held a meeting in April 2017 to discuss and propose recommendations for the evaluation and management of quality of life in MPS patients in Latin America. In the light of this scenario, the present work summarizes the content of the discussions and presents the recommendations produced at the meeting. The panel had suggested the use of the following tools for the assessment of health-related quality of life (HRQoL): Children's Health Assessment Questionnaire (CHAQ) for children and patients unable to express their feelings, Health Assessments Questionnaire (HAQ) and EuroQol 5 Domains (EQ-5D) scales for adult patients. Based on the scores verified in these scales, the panel proposes interventions that aim reducing the impairment of the quality of life in patients with MPS disorders.

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

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