Clinical features and management of arterial hypertension in children with Williams–Beuren syndrome
Nephrol Dial Transplant (2010) 25: 434–438
doi: 10.1093/ndt/gfp522
Advance Access publication 8 October 2009
Clinical features and management of arterial hypertension in children
with Williams–Beuren syndrome
Karim Bouchireb1 , Olivia Boyer1,2 , Damien Bonnet3 , Francis Brunelle4 , Stephane Decramer5 ,
Gilbert Landthaler6 , Aurelia Liutkus7 , Patrick Niaudet1,2 and Rémi Salomon1,2
1
Department of Pediatric Nephrology, Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Hôpital
Necker–Enfants Malades, Paris, 2 Université Paris Descartes, Faculté de médecine, France, 3 Department of Pediatric Cardiology,
4
Department of Pediatric Radiology, Hôpital Necker–Enfants Malades, Paris, 5 Department of Pediatric Nephrology, Hôpital
D’Enfants, Toulouse, 6 Department of Pediatric Nephrology, Hôpital Charles Nicolle, Rouen and 7 Department of Pediatric
Nephrology, Hôpital Femmes Mère Enfants, Lyon, France
Correspondence and offprint requests to: Rémi Salomon; E-mail:
Abstract
Background. Hypertension is a common finding in children with Williams–Beuren syndrome (WBS).
Methods. The aim of this retrospective study was to review the clinical presentation of systemic hypertension in
WBS children, its origin and management. We included 41
children with confirmed WBS who were referred to the
paediatric nephrology or cardiology unit for hypertension.
Results. The mean age at diagnosis of hypertension was
4.7 years. Out of 41, 24 patients had systolic blood pressure (BP) between +10 and +30 mmHg above the 95th
percentile (1.645 SD), and 20/41 patients had diastolic BP
between the 95th percentile (1.645 SD) and >10 mmHg.
Thirty-nine patients were asymptomatic. Arteriography,
performed in 17/41 patients, revealed a renal artery stenosis (RAS) in 10 patients (58%). Echocardiography was performed in all patients and showed isthmic coarctation in
four patients (9%). Calcium channel blockers were used in
half of the patients (22/41) and seemed to control hypertension in most cases. Interventional treatment of RAS was
performed in five patients (three angioplasty and two surgical bypass). It controlled hypertension in one patient but
remained ineffective in the four others.
Conclusions. Medical treatment essentially calcium blockers improved hypertension in most cases. Interventional
treatment of RAS has not been encouraging.
Keywords: arterial hypertension; renal artery stenosis;
Williams–Beuren syndrome
Introduction
Williams–Beuren syndrome (WBS) (OMIM # 194050) is
caused by a heterozygous microdeletion of the chromosome
region 7q11.23, including among others the elastin gene.
The main clinical features include a distinctive facial appearance with elfin facies, mental and statural deficiencies,
cardiovascular abnormalities (commonly supravalvular aortic stenosis) and occasionally infantile hypercalcaemia [1].
WBS children are also at risk for systemic hypertension,
with a frequency ranging from 5 to 70% in the literature
(Table 1). A clear aetiology is found in only a minority
of patients including renal artery stenosis (RAS) and/or
diffuse aortic narrowing and/or aortic coarctation. The vascular lesions in WBS seem to be linked to reduced elastin
synthesis and increased proliferation of vascular smooth
muscle cells [2], but the exact pathways connecting the
elastin deficiency to increased vascular cell proliferation
are still unknown.
Pathological vascular lesions in WBS include increased
intima–media thickness with thick irregular elastic fibres,
swirling collagen and hypertrophied smooth muscle cells.
However, the compliance of the large elastic arteries is not
modified in these patients [8]. There are few data on the
clinical characteristics and management of hypertension in
these children. We report on a multicentric retrospective
study including 41 WBS patients with systemic hypertension. Our aim was to study the clinical presentation and the
aetiologic investigations of hypertension on the one hand
and to evaluate the medical or endovascular management
on the other hand.
Patients and methods
Clinical and biological data
A total of 19 paediatric nephrology units in France, Belgium and Canada
were invited to participate in this retrospective study. A questionnaire for
all children aged 20 years or less with a diagnosis of WBS associated with
hypertension was filled. Thirteen centres (11 in France, 1 in Belgium and
1 in Canada) provided clinical information concerning 41 WBS patients
referred for systemic hypertension between 1990 and 2008. Hypertension
was defined for patients aged ≤ 17 years as average systolic BP (SBP)
and/or diastolic BP (DBP) ≥ 95th percentile for gender, age and height
on ≥3 occasions, based upon the 2004 National High Blood Pressure
Education Program Working Group (NHBPEP) [3]. For patients aged
>17 years at diagnosis, hypertension was defined as SBP ≥ 140 mmHg
and/or DBP ≥ 90 mmHg [4]. BP was rarely reported of both arms which
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Clinical features and management of arterial hypertension in children with Williams Beuren syndrome
Table 1. Prevalence of arterial hypertension in Williams–Beuren syndrome: a review of the literature
Prevalence of
hypertension
Age of patients (years)
References
7/42 (17%)
19/32 (59%)
7/10 (70%)
2/40 (5%)
19/45 (42.2%)
8/20 (40%)
6/13 (46%)
9/21 (42%)
17/25 (68%)
23/42 (55%)
12/20 (60%)
3/20 (15%)
26/57 (45%)
7/22 (31%)
<16
16–48 (median 19)
>18
10.5 and 17
0.1–34 (median 6.5)
>10
10–18
3.5–19
2.4–26.1 (median 11.5)
>15
30–51 (median 38.8)
11.4 and 16
<28
<39 (median 9.7)
Morris et al. [1]
Ingelfinger et al. [11]
Lopez Rangel et al. [16]
Pober et al. [10]
Wessel et al. [9]
Broder et al. [17]
Aggoun et al. [8]
Rose et al. [12]
Eronen et al. [13]
Cherniske et al. [18]
Sugayama et al. [19]
Del Campo et al. [20]
Ferrero et al. [14]
would have eliminated the Coanda effect related to supravalvular aortic stenosis that may cause elevated BP only in the right arm [15]. The
patient’s medical history was reviewed with emphasis on the occurrence
of hypertension, including age, circumstances of diagnosis, BP measurements and symptoms related to hypertension. Left ventricular hypertrophy
on initial echocardiography was noted. Other main features of WBS such
as congenital heart defects and mental retardation were also noted. For
each patient, serum creatinine values and total calcaemia from the diagnosis of WBS until the last follow-up were recorded. Hypercalcaemia
was defined as a serum calcium >2.75 mmol/l. Renal function assessed by
estimated glomerular filtration rate (eGFR) according to the Schwartz formula was recorded, and renal insufficiency was defined as eGFR < 75 ml/
min/1.73 m2 .
Radiological findings
Data from kidney ultrasonography (US) performed when hypertension was
diagnosed were recorded. Doppler US of renal artery, CT angiography and
convent (...truncated)
