Although the clinical manifestations of membranous supravalvular aortic stenosis (SVAS) are distinctive, its diagnosis remains challenging. Failure to initiate surgical treatment in a timely manner greatly increases the risk of sudden cardiac death. We report a case of membranous SVAS, detailing the clinical presentation and imaging manifestations.

Elastin-driven genetic diseases are a group of complex diseases driven by elastin protein insufficiency and dominant-negative production of aberrant protein, including supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. Here, a Chinese boy with a novel nonsense mutation in the ELN gene is reported.
We report a 1-year-old boy who presented with exercise intolerance, weight growth restriction with age, a 1-year history of heart murmur, and inguinal hernia. Gene sequencing revealed a novel nonsense mutation in the ELN gene (c.757 C > T (p.Gln253Ter), NM_000501.4). Due to severe branch pulmonary artery stenosis, the reconstruction of the branch pulmonary artery with autologous pericardium was performed. The inguinal hernia repair was performed 3 months postoperatively. After six months of outpatient follow-up, the child recovered well, gained weight with age, and had no special clinical symptoms.
We identified a de novo nonsense mutation in the ELN gene leading to mild SVAS and severe branch pulmonary artery stenosis. A new phenotype of inguinal hernia was also needed to be considered for possible association with the ELN gene. Still, further confirmation will be necessary.

Williams syndrome (WS) is a multisystem neurodevelopmental disorder caused by microdeletions in 7q11.23. This study aims to characterize the clinical phenotypes of Chinese children with WS to help for the early diagnosis and intervention of this disease.
231 children diagnosed with WS were retrospectively recruited to the study. Clinical data were analyzed to obtain the incidence of different clinical phenotypes. The occurrence of phenotypes and the influence of gender and age on the incidence of different phenotypes were analyzed.
All WS exhibited facial dysmorphism (100.0%). The majority had neurodevelopmental disorder (91.8%), hoarseness (87.4%) and cardiovascular anomalies (85.7%). The incidence of short stature (46.9%), inguinal hernia (47.2%), hypercalciuria (29.10%), hypercalcemia (9.1%), subclinical hypothyroidism (26.4%) and hypothyroidism (7.4%) were relatively higher. Gender differences were found in supravalvular aortic stenosis (SVAS, p < .001), ventricular septal defect (VSD, p < .05), inguinal hernia (p < .001), superior pulmonary stenosis (SVPS, p < .05) and neurodevelopmental disorder (p < .05). The incidence of neurodevelopmental disorder in WS increased with age (p < .05) while cardiovascular anomalies (p < .001), short stature (p < .001), hypercalciuria (p < .001) and hypercalcemia (p < .01) decreased with age.
Facial dysmorphism, neurodevelopmental disorder, hoarseness and cardiovascular anomalies were the most common phenotypes. Genetic testing should be suggested to confirm the diagnosis for children with the above abnormalities. Gender and age should be taken into account when making diagnosis and intervention.

BACKGROUND: Supravalvular aortic stenosis (SVAS) and congenital discontinuity of right coronary artery are both rare congenital cardiovascular abnormalities. This is the first case report about SVAS that occurred with the congenital discontinuity of right coronary artery.
METHODS: A 3-month-old female infant presented with aortic stenosis at sinotubular level and congenital right coronary artery deficiency. According to cardiovascular CT results, Doty technique was adopted to restore the aortic root geometry under cardiopulmonary bypass. An angioplasty was performed to establish right coronary blood flow at the same time. The patient had no abnormal cardiac symptoms after surgery. The postoperative echocardiogram revealed a normal laminar flow of the right coronary artery into the right coronary sinus, normal aortic blood flow and normal myocardial functions.
CONCLUSIONS: SVAS is characterized by the stenosis of the lumen of the ascending aorta above the aortic valve. Congenital discontinuity of RCA is probably related to dysplasia or congenital occlusion of the RCA during the development of embryo. This kind of malformation may lead to the deficiency of blood supply in sinoatrial and atrioventricular node, eventually causing their dysfunction, which usually leads to arrhythmias as the main manifestations. Angioplasty can improve blood supply of the heart without increasing the risk of major complications, and perioperative prognosis revealed good. This case image also suggested that cardiovascular CT can provide excellent visualization of complex vascular anatomies.
CONCLUSIONS: We reported this rare combination of malformations consisted of SVAS and discontinuity of right coronary artery. We treated this patient with the Doty technique and angioplasty procedures.

Williams syndrome (WS) is a rare congenital developmental disorder caused by the deletion of between 26 and 28 genes on chromosome 7q11.23. For patients with WS, in view of the particularity of the supravalvular aortic stenosis, choosing appropriate arterial cannula, maintaining higher perfusion pressure as well as strengthening myocardial protection during cardiopulmonary bypass (CPB) is essential to the clinical outcome. Here, we report a child with pulmonary artery valvular stenosis who failed to wean off CPB because of malignant arrhythmias and cardiac insufficiency after surgical correction of pulmonary valvular stenosis. With the assistance of extracorporeal membrane oxygenation (ECMO), emergency cardiac catheterization revealed supravalvular aortic stenosis (SVAS), which suggests a suspected missed diagnosis of WS. Finally, under the support of ECMO, the cardiac function gradually returned to normal, and the child was discharged 23 days after surgery.

We compared differences in the hemodynamic parameters of multiple surgical techniques for supravalvular aortic stenosis (SVAS). A three-dimensional model was reconstructed based on a patient\'s CT scan. Virtual McGoon, Doty, and Brom repairs were completed using computer-aided design (CAD). Hemodynamic parameters were calculated through computational fluid dynamics (CFD). The velocity profile and wall shear stress (WSS) showed the blood flow pattern. Energy loss (EL) and energy efficiency (EE) were calculated to estimate the cardiac workload. The perioperative blood flow ratio (BFR) of brachiocephalic vessels and coronary arteries was calculated. The preoperative flow velocity was abnormally high (> 5.0 m/s). High WSS was detected at the sinotubular junction (STJ), and its preoperative distribution in the aorta was uneven. High-speed flow disappeared after each of the three operations. The WSS distribution at the aortic root was consistent with the postoperative STJ structure of each operation. EL in the systolic phase decreased postoperatively (Original: 634 mW, McGoon: 218 mW, Doty: 278 mW, Brom: 255 mW). No significant difference in brachiocephalic BFR was detected among the different techniques. A slightly increased coronary BFR (Original: 7.56%, McGoon: 7.99%, Doty: 8.55%, Brom: 8.89%) was detected. McGoon, Doty, and Brom repair each effectively restored stable blood flow and greatly improved EE. The best WSS distribution and coronary blood supply were achieved after Brom repair due to its ability to reconstruct the symmetrical aortic root structure. CFD combined with a virtual operation is a promising method in surgical planning and optimization for SVAS.

Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p <0.001). This result was further confirmed in the multivariable Cox regression models. After adjusting for age, sex, low density lipoprotein cholesterol (LDL_C)-year-score, lipid-lowering drugs, cardiovascular disease, and carotid artery plaque, SVAS was an independent risk factor of premature death in HoFH on the multivariate analysis (hazard ratio 4.45; 95% confidence interval, 1.10 to 18.12; p = 0.037). In conclusion, a significantly increased risk of premature death was observed in HoFH patients with SVAS. Our study emphasized the importance of careful and aggressive management in these patients when appropriate.

OBJECTIVE: To explore the genetic basis for a child with supravalvular aortic stenosis.
METHODS: The child and his parents were subjected to conventional G-banding karyotyping, array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis.
RESULTS: No karyotypic abnormality was detected in the child and his parents. aCGH has identified a de novo 278 kb deletion encompassing the ELN gene in 7q11.23, which overlapped with the critical region of Williams-Beuren syndrome (WBS). MLPA has confirmed above findings.
CONCLUSIONS: The proband was diagnosed with atypical WBS. Deletion of the ELN gene may predispose to supravalvular aortic stenosis in the proband.

暂无摘要。

Supravalvular aortic stenosis (SVAS) represents a heterogeneous group, including Williams syndrome, familial elastin arteriopathy, sporadic cases, and others. This study sought to evaluate long-term outcomes of SVAS repair.
A total of 87 patients underwent surgical repair of congenital SVAS at Boston Children\'s Hospital in Boston, Massachusetts, between 1997 and 2017. A total of 41 patients had Williams syndrome, and 46 did not. Of the 46 patients who did not have Williams syndrome, 23 had sporadic SVAS, and 13 had familial elastin arteriopathy. Demographic data and outcomes were reviewed and analyzed from medical records.
The median age at operation was 2.9 years. Mean z score of the sinotubular junction was -3.29 ± 1.42 and of the aortic root was -0.09 ± 1.19. A total of 26% (n = 22) patients had coronary ostium stenosis, and 41% (n = 9) of them required patch plasty. Survival rates at 5, 10, and 20 years were all 94.3%. Freedom from left ventricular outflow tract reoperation at 5, 10, and 20 years was 78.5%, 70.3%, and 70.3%, respectively. Freedom from aortic arch reintervention at 5, 10, and 20 years was 98.6%, 94.3%, 89.3%, respectively. In risk factors analysis, age younger than 1 year, z scores of the aortic valve and aortic root, and concomitant right ventricular outflow tract surgical repair were predictive of the need for reoperation and reintervention for left or right ventricular outflow tract obstruction.
Excellent long-term survival rates can be achieved with surgical repair of SVAS. Age younger than 1 year, small aortic valve and aortic root z scores, and concomitant right ventricular outflow tract surgical repair were predictors of reoperation and reintervention.