Abstract
BackgroundInsufficient elastin synthesis leads to vascular complications and arterial hypertension in children with Williams-Beuren syndrome. Restoring sufficient quantity of elastin should then result in prevention or inhibition of vascular malformations and improvement in arterial blood pressure.MethodsThe aim of this study was to assess the efficacy and safety of minoxidil on Intima Media Thickness (IMT) on the right common carotid artery after twelve-month treatment in patient with Williams-Beuren syndrome. We performed a randomized placebo controlled double blind trial. All participants were treated for 12 months and followed for 18 months. The principal outcome was assessed by an independent adjudication committee blinded to the allocated treatment groups.ResultsThe principal outcome was available for 9 patients in the placebo group and 8 patients in the minoxidil group. After 12-month treatment, the IMT in the minoxidil group increased by 0.03 mm (95% CI -0.002, 0.06) compared with 0.01 mm (95%CI - 0.02, 0.04 mm) in the placebo group (p = 0.4). Two serious adverse events unrelated to the treatment occurred, one in the minoxidil and 1 in the placebo group. After 18 months, the IMT increased by 0.07 mm (95% CI 0.04, 0.10 mm) in the minoxidil compared with 0.01 mm (95% CI -0.02, 0.04 mm) in the placebo group (p = 0.008).ConclusionOur results suggest a slight increase after 12 and 18-month follow-up in IMT. More understanding of the biological changes induced by minoxidil should better explain its potential role on elastogenesis in Williams-Beuren syndrome.Trials registrationUS National Institutes of Health Clinical Trial Register (NCT00876200). Registered 3 April 2009 (retrospectively registered).
Highlights
Insufficient elastin synthesis leads to vascular complications and arterial hypertension in children with Williams-Beuren syndrome
Four in the minoxidil and 6 in the placebo group had a previous history of cardiovascular diseases, and four were treated for hypertension (2 received ACE inhibitors in the minoxidil and 2 received Beta blockers in the minoxidil group)
The principal outcome was available for 9 patients in the placebo group and 8 patients in the minoxidil group (Fig. 1)
Summary
Insufficient elastin synthesis leads to vascular complications and arterial hypertension in children with Williams-Beuren syndrome. WBS is due to a 7q11.23 micro-deletion [4,5,6,7] This deletion encompasses several genes including the gene encoding for elastin (ELN), a protein found in fibroblasts and the smooth muscle fibres of blood vessels. ELN haploinsufficiency causes vascular abnormalities, such as supra-valvular aortic stenosis (SVAS) [8], which correspond to a thickening of the vessel wall. Mutations in the ELN have been found in a number of patients having isolated SVAS or stenosis of other large arteries [9]. Polymorphisms of the ELN gene may cause a number of vascular diseases, including hypertension, atherosclerosis, and stenosis [8, 19]
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