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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Dailey-Schwartz, AL; Tadros, HJ; Azamian, MS; Lalani, SR; Morris, SA; Allen, HD; Kim, JJ; Landstrom, AP

Published Date

  • November 2018

Published In

Volume / Issue

  • 202 /

Start / End Page

  • 206 - 211.e2

PubMed ID

  • 30172441

Pubmed Central ID

  • PMC6203622

Electronic International Standard Serial Number (EISSN)

  • 1097-6833

Digital Object Identifier (DOI)

  • 10.1016/j.jpeds.2018.07.022


  • eng

Conference Location

  • United States