Copy Number Variants of Undetermined Significance Are Not Associated with Worse Clinical Outcomes in Hypoplastic Left Heart Syndrome.
Abstract
OBJECTIVE:To determine the prevalence, spectrum, and prognostic significance of copy
number variants of undetermined significance (cnVUS) seen on chromosomal microarray
(CMA) in neonates with hypoplastic left heart syndrome (HLHS). STUDY DESIGN:Neonates
with HLHS who presented to Texas Children's Hospital between June 2008 and December
2016 were identified. CMA results were abstracted and compared against copy number
variations (CNVs) in ostensibly healthy individuals gathered from the literature.
Findings were classified as normal, consistent with a known genetic disorder, or cnVUS.
Survival was then compared using Kaplan-Meier analysis. Secondary outcomes included
tracheostomy, feeding tube at discharge, cardiac arrest, and extracorporeal membrane
oxygenation (ECMO). RESULTS:Our study cohort comprised 105 neonates with HLHS, including
70 (66.7%) with normal CMA results, 9 (8.6%) with findings consistent with a known
genetic disorder, and 26 (24.7%) with a cnVUS. Six of the 26 (23.0%) neonates with
a cnVUS had a variant that localized to a specific region of the genome seen in the
healthy control population. One-year survival was 84.0% in patients with a cnVUS,
68.3% in those with normal CMA results, and 33.3% in those with a known genetic disorder
(P = .003). There were no significant differences in secondary outcomes among the
groups, although notably ECMO was used in 15.7% of patients with normal CMA and was
not used in those with cnVUS and abnormal results (P = .038). CONCLUSIONS:Among children
with HLHS, cnVUSs detected on CMA are common. The cnVUSs do not localize to specific
regions of the genome, and are not associated with worse outcomes compared with normal
CMA results.
Type
Journal articleSubject
HumansHypoplastic Left Heart Syndrome
Prognosis
Palliative Care
Extracorporeal Membrane Oxygenation
Cardiac Surgical Procedures
Cause of Death
Risk Assessment
Survival Analysis
Retrospective Studies
Cohort Studies
Infant, Newborn
Hospitals, Pediatric
Texas
Female
Male
DNA Copy Number Variations
Kaplan-Meier Estimate
Permalink
https://hdl.handle.net/10161/20301Published Version (Please cite this version)
10.1016/j.jpeds.2018.07.022Publication Info
Dailey-Schwartz, Andrew L; Tadros, Hanna J; Azamian, Mahshid Sababi; Lalani, Seema
R; Morris, Shaine A; Allen, Hugh D; ... Landstrom, Andrew P (2018). Copy Number Variants of Undetermined Significance Are Not Associated with Worse Clinical
Outcomes in Hypoplastic Left Heart Syndrome. The Journal of pediatrics, 202. pp. 206-211.e2. 10.1016/j.jpeds.2018.07.022. Retrieved from https://hdl.handle.net/10161/20301.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Andrew Paul Landstrom
Associate Professor of Pediatrics
Dr. Landstrom is a physician scientist who specializes in the care of children and
young adults with arrhythmias, heritable cardiovascular diseases, and sudden unexplained
death syndromes. As a clinician, he is trained in pediatric cardiology with a focus
on arrhythmias and genetic diseases of the heart. He specializes in caring for patients
with heritable arrhythmia (channelopathies) such as long QT syndrome, Brugada syndrome,
catecholaminergic polymorphic ventricular tachycardia,

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info