Background:Elastin insufficiency causes recurrent vascular stenoses. Hemizygous deletion of the elastin gene (ELN) causes Williams-Beuren syndrome (WBS), while single nucleotide variants in ELN cause nonsyndromic supravalvar aortic stenosis (SVAS). Our objective was to compare cardiovascular disease outcomes in patients with WBS and nonsyndromic SVAS.Methods:Patients (81 WBS, 42 nonsyndromic SVAS) with cardiovascular disease were included in this retrospective single center study. Freedom from surgical and catheter interventions and reinterventions was compared. Vascular tissue from 8 patients and 6 controls was analyzed for arterial wall architecture.Results:Patients with nonsyndromic SVAS presented at a younger age (median 0.3 [0.4–0.7] years) compared with patients with WBS (1.3 [0.2–3.0] years) and had lower freedom from surgical/catheter interventions compared with patients with WBS, with median event-free survival 1.1 (0.3–5.9) versus 4.7 (2.4–13.3) years, respectively (hazard ratio, 1.62 [95% CI, 1.02–2.56]; P=0.04). Patients with nonsyndromic SVAS also had a lower freedom from reinterventions (P=0.054 by log-rank test). This was related in part to a higher frequency of primary and reinterventions for concomitant valvar aortic stenosis. Histology revealed abnormal intimal and medial thickening, disorganized and fragmented elastic fibers, reduced smooth muscle calponin expression, and increased macrophage marker, CD68, expression in the arterial walls in patients with WBS and nonsyndromic SVAS compared with controls.Conclusions:Patients with nonsyndromic SVAS require early and more frequent vascular and valvular interventions and reinterventions, in particular for concomitant valvar aortic stenosis compared with patients with WBS. This provides important prognostic information to guide counseling of affected families with cardiovascular disease and may guide primary intervention strategies based on predicted risk of restenosis.

中文翻译：

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弹性蛋白动脉病患者的基因诊断和心血管表型的严重程度。

背景：弹性蛋白不足会导致复发性血管狭窄。弹性蛋白基因 ( ELN ) 的半合子缺失导致 Williams-Beuren 综合征 (WBS)，而ELN 中的单核苷酸变异导致非综合征性瓣上主动脉瓣狭窄 (SVAS)。我们的目标是比较 WBS 和非综合征 SVAS 患者的心血管疾病结局。方法：这项回顾性单中心研究包括患有心血管疾病的患者（81 名 WBS，42 名非综合征 SVAS）。比较了免于手术和导管干预以及再干预的情况。分析了 8 名患者和 6 名对照组的血管组织的动脉壁结构。 结果：与 WBS 患者（1.3 [0.2-3.0] 岁）相比，非综合征性 SVAS 患者的年龄（中位数为 0.3 [0.4-0.7] 岁）更年轻与 WBS 患者相比，手术/导管干预的自由度较低，中位无事件生存期分别为 1.1 (0.3–5.9) 年和 4.7 (2.4–13.3) 年（风险比，1.62 [95% CI，1.02–2.56） ];P = 0.04）。非综合征 SVAS 患者的再干预自由度也较低（P=0.054 通过对数秩检验）。这在一定程度上与对伴随的主动脉瓣狭窄进行初次和再干预的频率较高有关。组织学显示，与对照组相比，WBS 和非综合征 SVAS 患者的动脉壁内膜和中层增厚异常，弹性纤维紊乱和破碎，平滑肌钙调蛋白表达降低，巨噬细胞标志物 CD68 表达增加。 结论：非综合征 SVAS 患者需要早期和更频繁的血管和瓣膜干预和再干预，特别是与 WBS 患者相比，伴发的主动脉瓣狭窄。这提供了重要的预后信息，以指导患有心血管疾病的受影响家庭的咨询，并可能指导基于再狭窄预测风险的主要干预策略。