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The frequency and efficacy of genetic testing in individuals with scimitar syndrome

Published online by Cambridge University Press:  02 July 2021

Tyler A. Fick
Department of Pediatrics, Section of Pediatric Cardiology, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas, USA
Daryl A. Scott
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA
Philip J. Lupo
Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA
Justin Weigand
Department of Pediatrics, Section of Pediatric Cardiology, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas, USA
Shaine A. Morris*
Department of Pediatrics, Section of Pediatric Cardiology, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas, USA
Author for correspondence: Shaine A. Morris, MD, MPH, Department of Pediatrics, Section of Pediatric Cardiology, Texas Children’s Hospital and Baylor College of Medicine, 6651 Main St, Legacy Tower, E1920, Houston, Texas, USA. Tel: 832–824–8278. E-mail:



Scimitar syndrome is a rare CHD composed of partial anomalous pulmonary venous connection from the right lung, via a scimitar vein, to the inferior vena cava rather than the left atrium. Genetic conditions associated with scimitar syndrome have not been well investigated at present.


Our study included patients with scimitar syndrome diagnosed at Texas Children’s Hospital from January 1987 to July 2020. Medical records were evaluated to determine if genetic testing was performed, including chromosomal microarray analysis or whole-exome sequencing. Copy number variants identified as pathogenic/likely pathogenic and variants of unknown significance were collected. Analyses of cardiac and extracardiac findings were performed via chart review.


Ninety-eight patients were identified with scimitar syndrome, 89 of which met inclusion criteria. A chromosome analysis or chromosomal microarray analysis was performed in 18 patients (20%). Whole-exome sequencing was performed in six patients following negative chromosomal microarray analysis testing. A molecular genetic diagnosis was made in 7 of 18 cases (39% of those tested). Ninety-six per cent of the cohort had some type of extracardiac finding, with 43% having asthma and 20% having a gastrointestinal pathology. Of the seven patients with positive genetic testing, all had extracardiac anomalies with all but one having gastrointestinal findings and 30% having congenital diaphragmatic hernia.


Genetic testing revealed an underlying diagnosis in roughly 40% of those tested. Given the relatively high prevalence of pathogenic variants, we recommend chromosomal microarray analysis and whole-exome sequencing for patients with scimitar syndrome and extracardiac defects.

Original Article
© The Author(s), 2021. Published by Cambridge University Press

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