Copy Number Variants of Undetermined Significance Are Not Associated with Worse Clinical Outcomes in Hypoplastic Left Heart Syndrome.

Dailey-Schwartz, Andrew L

Tadros, Hanna J

Azamian, Mahshid Sababi

Lalani, Seema R

Morris, Shaine A

Allen, Hugh D

Kim, Jeffrey J

Landstrom, Andrew P

2020-04-01T13:29:51Z

2020-04-01T13:29:51Z

2018-11

2020-04-01T13:29:50Z

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.

S0022-3476(18)30915-6

0022-3476

1097-6833

https://hdl.handle.net/10161/20301

eng

Elsevier BV

The Journal of pediatrics

10.1016/j.jpeds.2018.07.022

Humans

Hypoplastic 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

Copy Number Variants of Undetermined Significance Are Not Associated with Worse Clinical Outcomes in Hypoplastic Left Heart Syndrome.

Journal article

Landstrom, Andrew P|0000-0002-1878-9631

206

211.e2

School of Medicine

Cell Biology

Pediatrics, Cardiology

Duke

Basic Science Departments

Pediatrics

Clinical Science Departments

Published

202