Cardiovascular system involvement is quite common and the leading cause of morbidity and mortality in patients with Williams syndrome (WS), most of whom need surgery. The present study aimed to provide a detailed evaluation of the features of surgical procedures and outcomes of patients with WS given as single-center experience, and additionally to make a detailed review from Türkiye.
Thirty-five children with WS diagnosed between the years 1992 and 2021 were evaluated retrospectively including cardiovascular data, surgical treatment features, and outcomes. A total of six articles from Türkiye were evaluated.
A total of 35 patients with Williams Syndrome (24 male) with a median age of cardiologic diagnosis of 6 months (range, 2 days-6 years) were evaluated. The cardiac defects of the patients with WS were found as supravalvular aortic stenosis (SVAS) (n=30, 85%) and peripheral pulmonary stenosis (PPS) (n=21, 65%). Additional cardiac anomalies were seen in 71% patients. The rate of SVAS and PPS surgery in all patients with WS was 77.1%. The median surgical age of the patients was 2.5 years (range, 7 months-15.5 years). No patients died due to surgery. But one patient died because of ventricular tachycardia due to anesthesia at the beginning of angiography. A total of 138 (63% male) patients with WS were evaluated from the articles published in Türkiye. Of 138 patients, 64.4% had SVAS, 52.1% had PPS, and 39.8% had additional cardiac anomaly. The median follow-up period ranged from 17 months to 18 years, and six (4.3%) patients died in the early postoperative period.
Cardiovascular system involvement is extremely common and is the leading cause of morbidity and mortality in patients with WS, often requiring surgical intervention. As seen in our study including 35 patients with WS and in publications from Türkiye, SVAS in patients with WS generally requires surgery, especially in the first year of life. PPS, on the other hand, requires surgery less frequently than SVAS, and pulmonary stenosis appears to decrease over time.

OBJECTIVE: Congenital supravalvular aortic stenosis (SVAS) is a rare form of congenital outflow tract obstruction and long-term outcomes are scarcely reported. This study aims to provide an overview of outcomes after surgical repair for congenital SVAS.
METHODS: A systematic review of published literature was conducted, including observational studies reporting long-term clinical outcome (>2 years) after SVAS repair in children or adults considering >20 patients. Early risks, late event rates and time-to-event data were pooled and entered into a microsimulation model to estimate 30-year outcomes. Life expectancy was compared to the age-, sex- and origin-matched general population.
RESULTS: Twenty-three publications were included, encompassing a total of 1472 patients (13 125 patient-years; pooled mean follow-up: 9.0 (6.2) years; median follow-up: 6.3 years). Pooled mean age at surgical repair was 4.7 (5.8) years and the most commonly used surgical technique was the single-patch repair (43.6%). Pooled early mortality was 4.2% (95% confidence interval: 3.2-5.5%) and late mortality was 0.61% (95% CI: 0.45-0.83) per patient-year. Based on microsimulation, over a 30-year time horizon, it was estimated that an average patient with SVAS repair (mean age: 4.7 years) had an observed life expectancy that was 90.7% (95% credible interval: 90.0-91.6%) of expected life expectancy in the matched general population. The microsimulation-based 30-year risk of myocardial infarction was 8.1% (95% credible interval: 7.3-9.9%) and reintervention 31.3% (95% credible interval: 29.6-33.4%), of which 27.2% (95% credible interval: 25.8-29.1) due to repair dysfunction.
CONCLUSIONS: After surgical repair for SVAS, 30-year survival is lower than the matched-general-population survival and the lifetime risk of reintervention is considerable. Therefore, lifelong monitoring of the cardiovascular system and in particular residual stenosis and coronary obstruction is recommended.

UNASSIGNED: Williams syndrome (WS) results from a microdeletion that usually involves the elastin gene, leading to generalized arteriopathy. Cardiovascular anomalies are seen in 80% of WS patients, including supravalvular aortic stenosis (SVAS), pulmonary artery stenosis (PAS), and pulmonary stenosis (PS). Sudden death associated with procedural sedation and in the perioperative period in WS children have been reported. This study aims to describe extracorporeal membrane oxygenation (ECMO) use in WS children, identify risk factors for hospital mortality of WS patients, and compare outcomes between WS children and non-WS children with SVAS, PAS, and PS.
UNASSIGNED: Children 0-18 years-old in the Extracorporeal Life Support Organization (ELSO) Registry with a primary or secondary diagnosis of WS, SVAS, PAS, or PAS were included.
UNASSIGNED: Included were 50 WS children and 1222 non-WS children with similar cardiac diagnoses. ECMO use increased over time in both groups (p = 0.93), with most cases occurring in the current era. WS children were younger (p = 0.004), weighed less (p = 0.048), had a pulmonary indication for ECMO (50% vs 10%, p < 0.001), and were placed more on high frequency ventilation (p < 0.001) than non-WS patients. Despite reporting a respiratory indication, most (84%) WS patients were placed on VA-ECMO. There were no significant differences between the two groups in terms of pre-ECMO cardiac arrest, ECMO duration, or reason for ECMO discontinuation. Both groups had a mortality rate of 48% (p = 1.00). No risk factors for WS mortality were identified.

Severe familial hypercholesterolemia (SFH) is characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) and severe early-onset cardiovascular disease if left untreated. We report on the decade-long therapeutic journey of a 15-year-old boy with SFH due to a severe compound heterozygous genotype. He presented at the age of 5 years with widespread xanthomas and LDL-C of 17.4 mmol/L. He was diagnosed with SFH, initially treated with colestyramine that was subsequently combined with simvastatin. At the age of 12 years, he was diagnosed to have supravalvular aortic stenosis and ezetimibe/atorvastatin was introduced in place of colestyramine/simvastatin. At the age of 14 years, he received triple therapy with evolocumab, initially at the recommended dose of 420 mg monthly and then reduced to 140 mg biweekly. Currently at the age of 15 years, he is on atorvastatin 40 mg ON, ezetimibe 10 mg OM, and evolocumab 140 mg biweekly, achieving LDL-C levels of 2.4 mmol/L. Genetic testing identified compound heterozygous mutations in the LDL receptor genes [c.(940 + 1_941-1) (1845 + 1_1846-1)dup] and exon 12, nucleotide c.1747 C > T, amino acid p.(His583Tyr). Medical management without lipoprotein apheresis can achieve target LDL-C in children with SFH. Our patient, who developed supravalvular aortic stenosis at the age of 12 years, needed early aggressive treatment when SFH guidelines and newer drugs for young children were unavailable. Our patient demonstrated that 140 mg biweekly of evolocumab has the same cholesterol-lowering effect as the recommended 420 mg monthly dose.