Language
English
Publication Date
4-16-2024
Journal
Journal of the American Heart Association
DOI
10.1161/JAHA.123.034048
PMID
38591341
PMCID
PMC11262489
PubMedCentral® Posted Date
4-9-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Background: We aimed to describe the frequency and yield of genetic testing in supravalvar aortic stenosis (SVAS) following negative evaluation for Williams-Beuren syndrome (WS).
Methods and results: This retrospective cohort study included patients with SVAS at our institution who had a negative evaluation for WS from May 1991 to September 2021. SVAS was defined as (1) peak supravalvar velocity of ≥2 meters/second, (2) sinotubular junction or ascending aortic Z score < -2.0, or (3) sinotubular junction Z score < -1.5 with family history of SVAS. Patients with complex congenital heart disease, aortic valve disease as the primary condition, or only postoperative SVAS were excluded. Genetic testing and diagnoses were reported. Of 162 patients who were WS negative meeting inclusion criteria, 61 had genetic testing results available (38%). Chromosomal microarray had been performed in 44 of 61 and was nondiagnostic for non-WS causes of SVAS. Sequencing of 1 or more genes was performed in 47 of 61. Of these, 39 of 47 underwent ELN sequencing, 20 of 39 (51%) of whom had a diagnostic variant. Other diagnoses made by gene sequencing were Noonan syndrome (3 PTPN11, 1 RIT1), Alagille syndrome (3 JAG1), neurofibromatosis (1 NF1), and homozygous familial hypercholesterolemia (1 LDLR1). Overall, sequencing was diagnostic in 29 of 47 (62%).
Conclusions: When WS is excluded, gene sequencing for SVAS is high yield, with the highest yield for the ELN gene. Therefore, we recommend gene sequencing using a multigene panel or exome analysis. Hypercholesterolemia can also be considered in individuals bearing the stigmata of this disease.
Keywords
Humans, Williams Syndrome, Aortic Stenosis, Supravalvular, Retrospective Studies, Genetic Testing, Aorta, cardiovascular, genetics, SVAS, Williams syndrome
Published Open-Access
yes
Recommended Citation
Stephens, Sara B; Novy, Tyler; Spurzem, Gabrielle N; et al., "Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome" (2024). Faculty and Staff Publications. 5224.
https://digitalcommons.library.tmc.edu/baylor_docs/5224
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons