PubMed · 13888213
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A DUEX, H HALL ERBACH, H H HILGER, M LEY, A SCHAEDE, P THURN. 1961. [Supravalvular aortic stenosis].. https://pubmed.ncbi.nlm.nih.gov/13888213/
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This study evaluates the course of supravalvular aortic stenosis (SVAS)-associated right ventricular outflow tract (RVOT) obstruction and the results of surgery in children. We reviewed the medical records of 24 patients diagnosed with SVAS at initial echocardiographic examination or during the following period of RVOT obstruction. Very mild SVAS was defined as a transvalvular Doppler peak systolic instantanous gradient (PSIG) less than 25 mmHg, mild stenosis as 25-49 mmHg, moderate stenosis as 50-75 mmHg, and severe stenosis as more than 75 mmHg. The mean age of the patients was 3.1 +/- 2.9 years (range, 7 days to 12.7 years), and 18 of the patients (72%) were male. Fifteen patients had Williams' syndrome. Seventeen patients (71%) were followed for a mean of 5.2 +/- 3.8 years (range, 7 months to 13.5 years). Among 17 patients with complete follow-up records, 1 (6%) had very mild, 5 (29%) mild, 3 (18%) moderate, and 3 (18%) severe aortic stenosis at initial echocardiographic examination. In a newborn patient with mild pulmonary valvular stenosis. SVAS became evident after 2 months and progressed rapidly. Supravalvular aortic stenosis was very mild in 4 patients (23%), mild in 3 (18%), moderate in 3 (18%), and severe in 7 (41%) at last echocardiographic examination. Of 17 patients who were followed, 11 (65%) had RVOT obstruction at initial echocardiographic examination. RVOT obstruction disappeared in 5 patients, regressed in 1 patient, and appeared in 1 patient over the follow-up period. Four patients underwent operation. It appears reasonable that patients with very mild and mild stenosis should be followed medically every 1 or 2 years and patients with moderate stenosis once a year. Newborns with SVAS should be followed for rapid progression of SVAS. In some patients, RVOT obstruction may disappear, and SVAS may develop in others with RVOT obstruction. Patients with RVOT obstruction (at the valvular, supravalvular, or peripheral pulmonary arterial level) should be evaluated carefully for development of SVAS at follow-up.
Supravalvular aortic stenosis (SVAS) is a congenital heart disease that can occur as an isolated autosomal-dominant condition or as part of the developmental disorder Williams-Beuren syndrome (WBS) and is caused by heterozygous genetic lesions involving the elastin (ELN) gene locus on chromosome 7ql 1.23. SVAS is one of many phenotypic features associated with the contiguous gene microdeletion disorder, WBS, and is caused by deletion of the ELN locus on one chromosome 7 homolog. Point mutations, chromosomal deletions, and translocation involving ELN have also been described in individuals with nonsyndromic SVAS. In addition, ELN is involved in the connective tissue disorder, autosomal-dominant cutis laxa, and has been implicated as a susceptibility gene for hypertension and intracranial aneurysms. The molecular analysis of ELN defects is, therefore, an area of significant interest. Genetic screening can be achieved using a variety of techniques to detect both mutations and gross chromosome rearrangements involving the ELN locus, providing the ability to screen families and individuals with SVAS and associated elastinopathies.
Supravalvular aortic stenosis (SVAS), an inherited vascular disease, is caused by mutations in the elastin gene (ELN). Our aim was to identify novel mutations of ELN and to determine the expression of ELN in patients with SVAS. For screening mutations in ELN, we performed PCR-directed sequence analysis with genomic DNA isolated from SVAS patients and control subjects. Expression of ELN at the mRNA and protein levels were assessed by real-time PCR and Western blot analyses, respectively, using primary skin fibroblast cultures established from SVAS patients and control subjects. We identified two novel mutations of ELN, G297_A308del and Q700X, in two unrelated Korean patients with isolated SVAS. G297_A308del occurred de novo while Q700X was derived maternally. In the patient with G297_A308, elastin expression was not significantly altered at the mRNA level, but was reduced to approximately 50% of the normal control at the protein level. The elastin expression levels in the patient with Q700X were reduced to <50% of the normal controls at both the mRNA and protein levels. Our findings confirm that functional haploinsufficiency of elastin is responsible for the pathogenesis associated with isolated SVAS across different ethnic backgrounds.