Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome

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 eval...

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Main Authors: Sara B. Stephens, Tyler Novy, Gabrielle N. Spurzem, Benjamin Jacob, Taylor Beecroft, Emily Soludczyk, Beth A. Kozel, Justin Weigand, Shaine A. Morris
Format: Article
Language:English
Published: Wiley 2024-04-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.123.034048
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author Sara B. Stephens
Tyler Novy
Gabrielle N. Spurzem
Benjamin Jacob
Taylor Beecroft
Emily Soludczyk
Beth A. Kozel
Justin Weigand
Shaine A. Morris
author_facet Sara B. Stephens
Tyler Novy
Gabrielle N. Spurzem
Benjamin Jacob
Taylor Beecroft
Emily Soludczyk
Beth A. Kozel
Justin Weigand
Shaine A. Morris
author_sort Sara B. Stephens
collection DOAJ
description 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.
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spelling doaj.art-a6f4c9205229419ba3cbb1d9115471732024-04-16T09:33:09ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-04-0113810.1161/JAHA.123.034048Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams SyndromeSara B. Stephens0Tyler Novy1Gabrielle N. Spurzem2Benjamin Jacob3Taylor Beecroft4Emily Soludczyk5Beth A. Kozel6Justin Weigand7Shaine A. Morris8Section of Cardiology, Department of Pediatrics Baylor College of Medicine, Texas Children’s Hospital Houston TXDivision of Community and General Pediatrics, Department of Pediatrics, McGovern Medical School The University of Texas Health Science Center Houston TXUniversity of Washington Medical Center Seattle WASection of Cardiology, Department of Pediatrics Baylor College of Medicine, Texas Children’s Hospital Houston TXSection of Cardiology, Department of Pediatrics Baylor College of Medicine, Texas Children’s Hospital Houston TXSection of Cardiology, Department of Pediatrics Baylor College of Medicine, Texas Children’s Hospital Houston TXTranslational Vascular Medicine Branch National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda MDSection of Cardiology, Department of Pediatrics Baylor College of Medicine, Texas Children’s Hospital Houston TXSection of Cardiology, Department of Pediatrics Baylor College of Medicine, Texas Children’s Hospital Houston TXBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.123.034048cardiovasculargeneticsSVASWilliams syndrome
spellingShingle Sara B. Stephens
Tyler Novy
Gabrielle N. Spurzem
Benjamin Jacob
Taylor Beecroft
Emily Soludczyk
Beth A. Kozel
Justin Weigand
Shaine A. Morris
Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardiovascular
genetics
SVAS
Williams syndrome
title Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome
title_full Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome
title_fullStr Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome
title_full_unstemmed Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome
title_short Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome
title_sort genetic testing for supravalvar aortic stenosis what to do when it is not williams syndrome
topic cardiovascular
genetics
SVAS
Williams syndrome
url https://www.ahajournals.org/doi/10.1161/JAHA.123.034048
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