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

ORIGINAL ARTICLE Diagnosis and management of systemic hypertension due to renovascular and aortic stenosis in patients with Williams-Beuren syndrome Erika Arai Furusawa, MD, PhD1 Camila Sanches Lanetzki Esposito, MD1 Rachel Sayuri Honjo, MD, PhD2 Lisa Suzuki, MD, PhD3 Gabriela Nunes Leal, PhD3 Chong Ae Kim, MD, PhD2 Benita Galassi Soares Schvartsman, MD, PhD1 1. Pediatric Nephrology Unit, Institute of Children, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, Brasil. 2. Genetics Unit, Institute of Children, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, Brasil. 3. Radiology Unit, Institute of Children, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, Brasil. http://dx.doi.org/10.1590/1806-9282.64.08.723 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 KEYWORDS: children, hypertension, renal artery stenosis, Williams-Beuren syndrome INTRODUCTION Williams-Beuren syndrome (WBS) is a genetic disorder characterized by facial dysmorphisms, congenital heart defects, growth retardation, infantile hypercalcemia, renal and vascular abnormalities, and intellectual disability1. Clinical diagnosis is usually performed during childhood when the typical facial changes and cognitive profile become more apparent1 (Figure 1). Genetic confirmation can be carried out using FISH2 (fluorescence in situ hybridization) or MLPA3 (multiplex ligation-dependent probe amplification), or microarray tests for identification of the causal microdeletion at 7q11.23. Urinary tract system abnormalities in WBS have been described in approximately 18% of patients4,5,6 and include renal DATE OF SUBMISSION: 18-Nov-2016 DATE OF ACCEPTANCE: 20-Nov-2016 CORRESPONDING AUTHOR: Erika Furusawa Hospital das Clínicas, Av. Dr. Eneas de Carvalho Aguiar, 647 05403-000, Cerqueira Cesar, São Paulo, Brasil E-mail: 723 REV ASSOC MED BRAS 2018; 64(8):723-728 DIAGNOSIS AND MANAGEMENT OF SYSTEMIC HYPERTENSION DUE TO RENOVASCULAR AND AORTIC STENOSIS IN PATIENTS WITH WILLIAMS-BEUREN SYNDROME ectopia, hydronephrosis, renal agenesis or hypoplasia, vesicoureteral reflux, and voiding dysfunction. Nephrocalcinosis, proteinuria, and chronic renal failure have also been reported in some cases series4,5,6 Cardiovascular abnormalities are also quite common in patients with WBS and have been observed in more than 80% of cases7,8. Supravalvular aortic stenosis (SVAS) is the most frequent abnormality, with an estimated incidence of 64%(9,10). Systemic arterial abnormalities include localized or diffuse narrowing of the thoracic or abdominal aorta, coronary, renal and other visceral arteries11,12. According to Lacolley et al.13 vascular injury in patients with WBS may be associated with reduced elastin synthesis and increased proliferation of vascular smooth muscle cells. Arterial hypertension arterial (SAH) is also observed with high prevalence in WBS14. In a minority of patients, renal artery stenosis, diffuse narrowing of the aorta, aortic coarctation or a combination of these abnormalities have been implicated4,5. Renal artery stenosis is usually found at the origin of the renal arteries7 (Figure 2). Nonetheless, there are few reports about the origin and management of SAH in WBS, and the diagnosis is often not made. This study aimed to describe the incidence of hypertension among 65 patients with WBS, as well as the diagnosis and management of hypertension due to renovascular or aortic stenosis. METHODS Clínicas of the Faculty of Medicine of the University of São Paulo were included in this study. All patients were diagnosed with WBS based on clinical findings and had the presence of the 7q11.23 microdeletion confirmed by the FISH (2) or MLPA test (with a specific kit for WBS) (3). Patients with blood pressure (BP) values at or above the 95th percentile for age, gender, and height confirmed on 3 different occasions15 were included in the study and followed prospectively. Clinical and laboratory parameters such as the age of onset of hypertension, associated symptoms, baseline BP, fundus examination, microalbuminuria/creatinine16 and calcium/creatinine ratio17 in spot urine samples, estimated creatinine clearance18, and serum ionized calcium were evaluated. All enrolled patients were initially investigated by Doppler echocardiography(DE) and renal ultrasound (RU) with color-flow Doppler sonography of the renal arteries (DS). Those with findings of renal artery stenosis19 or hypertension stage II15 with a normal DS underwent computed tomographic angiography (CTA)(20) and/or gadolinium-enhanced magnetic resonance angiography (MRA) of the aorta and renal vessels21. Patients with unclear diagnosis by CTA and/or MRA or who required vascular therapeutic intervention (angioplasty) underwent conventional angiography (CA). RESULTS Sixty-five patients who were being treated from 1993 to 2010 at the Pediatric Nephrology and Genetics Units at the Institute of Children, Hospital das Of the 65 patients with WBS included in this study, 21 (32%; mean age of 13.9 years, range: 5 months to 20 years, 13 males) had hypertension and FIGURE 1: Female patient, at age 9y4m, with facial characteristics of WBS: periorbital fullness, short nose, malar hypoplasia, long philtrum, and thick lips. FIGURE 2: Digital subtraction angiography demonstrates discreet stenosis of the abdominal aorta anda severe stenosis of the left and right renal arteries. Also note several collateral arteries from the aorta on the left side REV ASSOC MED BRAS 2018; 64(8):723-728 724 FURUSAWA, E. A. ET AL were submitted to further imaging studies. In this group, the mean age at WBS diagnosis was 5.2 years (ranging from 8 months t (...truncated)