Supravalvular aortic stenosis (ORPHA:3193)
A rare aortic malformation characterized by the narrowing of the aorta lumen (close to its origin) associated or not with stenosis of other arteries (branch pulmonary arteries, coronary arteries). This narrowing of the aorta or pulmonary branches may impede blood flow, resulting in heart murmur and ventricular hypertrophy (left ventricle in case of aorta involvement, right ventricle in case of pulmonary artery involvement).
Epidemiology
The incidence of supravalvular aortic stenosis (SVAS) is estimated at approximately 1 in 25 000 births and the mean prevalence in the general population at 1/7 500.
Clinical description
Clinical manifestations of SVAS include ejection systolic murmur and, in some cases, symptoms of chest pain or syncope. The electrocardiogram may indicate signs of a repolarisation disorder at rest and/or signs of ischemia after a stress test.
Etiology
The narrowing results from a thickening of the artery wall, which is not related to atherosclerosis. SVAS is caused by a mutation in the elastin gene (ELN), which is located on chromosome 7q11.23. In nearly all cases, ELN mutations disrupt elastin protein synthesis, resulting in a production deficit.
Diagnostic methods
The discovery of a systolic murmur may prompt a cardiological examination, potentially showing ventricular hypertrophy. Echocardiogram may indicate a progressive ''hourglass'' narrowing of the aorta and/or pulmonary artery lumen, specific to SVAS. Angiography by retrograde femoral arterial catheterization would allow a more precise diagnosis but it may be associated with risk if the stenosis is significant. Thus, in such cases scanning is preferred. CT scan can show the location and the severity of aorta narrowing.
Differential diagnosis
SVAS can be part of the Williams-Beuren syndrome caused by microdeletion of the 7q11-q23 region, including the elastin and many contiguous genes. SVAS associated with Williams-Beuren syndrome is identical to isolated SVAS, however Williams-Beuren syndrome is also associated with a characteristic face, behavioral disorders and hypercalcemia.
Antenatal diagnosis
In a family affected by SVAS, the progressive nature of the disease makes the identification of mutation carriers important for follow-up. Prenatal ultrasound examination can allow detection of the aortic or pulmonary supravalvular stenosis.
Genetic counseling
Except for the cases with Williams-Beuren syndrome, the disease is either sporadic or familial. In familial cases it is transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity within members of the same family.
Management and treatment
Regular follow-up is recommended (every 6 months for infants and each year in children) in order to monitor the evolution of the stenosis, which can be removed by surgery. Surgical repair is indicated only for significant stenosis.
Prognosis
The prognosis of SVAS depends on the severity of the lesion and on potential associated anomalies located on the aortic valve or coronary arteries. Predictors of worse outcomes and frequent surgical intervention are the presence of diffuse lesions compared to discrete stenosis or presence of associated aortic valve disease.

                            Last update: 
                            September 2020


                            - Expert reviewer(s): 
                            Pr Sylvie DI FILIPPO