Merla Giuseppe, Brunetti-Pierri Nicola, Piccolo Pasquale, Micale Lucia, Loviglio Maria Nicla
Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy.
Circ Cardiovasc Genet. 2012 Dec;5(6):692-6. doi: 10.1161/CIRCGENETICS.112.962860.
Supravalvular aortic stenosis is a systemic elastin (ELN) arteriopathy that disproportionately affects the supravalvular aorta. ELN arteriopathy may be present in a nonsyndromic condition or in syndromic conditions such as Williams-Beuren syndrome. The anatomic findings include congenital narrowing of the lumen of the aorta and other arteries, such as branches of pulmonary or coronary arteries. Given the systemic nature of the disease, accurate evaluation is recommended to establish the degree and extent of vascular involvement and to plan appropriate interventions, which are indicated whenever hemodynamically significant stenoses occur. ELN arteriopathy is genetically heterogeneous and occurs as a consequence of haploinsufficiency of the ELN gene on chromosome 7q11.23, owing to either microdeletion of the entire chromosomal region or ELN point mutations. Interestingly, there is a prevalence of premature termination mutations resulting in null alleles among ELN point mutations. The identification of the genetic defect in patients with supravalvular aortic stenosis is essential for a definitive diagnosis, prognosis, and genetic counseling.
主动脉瓣上狭窄是一种系统性弹性蛋白（ELN）动脉病，对主动脉瓣上的主动脉影响尤为严重。ELN动脉病可能存在于非综合征性疾病中，也可能存在于威廉姆斯-贝伦综合征等综合征性疾病中。解剖学发现包括主动脉和其他动脉（如肺动脉或冠状动脉分支）管腔的先天性狭窄。鉴于该疾病的全身性，建议进行准确评估，以确定血管受累的程度和范围，并规划适当的干预措施，只要出现血流动力学上有意义的狭窄就应进行干预。ELN动脉病在遗传上具有异质性，是由于7号染色体q11.23区域的ELN基因单倍剂量不足所致，原因是整个染色体区域的微缺失或ELN点突变。有趣的是，在ELN点突变中，导致无效等位基因的过早终止突变很常见。确定主动脉瓣上狭窄患者的基因缺陷对于明确诊断、预后和遗传咨询至关重要。
