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Array CGH as a first-tier test for neonates with congenital heart disease

Published online by Cambridge University Press:  06 November 2013

Kristine K. Bachman ,
Stephanie J. DeWard ,
Constantinos Chrysostomou ,
Ricardo Munoz  and
Suneeta Madan-Khetarpal
Kristine K. Bachman
Affiliation:
Department of Human Genetics, Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America
Stephanie J. DeWard
Affiliation:
Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Constantinos Chrysostomou
Affiliation:
Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Department of Critical Care Medicine, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America
Ricardo Munoz
Affiliation:
Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Department of Critical Care Medicine, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America
Suneeta Madan-Khetarpal*
Affiliation:
Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America
*
Correspondence to: Dr S. Madan-Khetarpal, MD, Department of Critical Care Medicine, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, FP Suite 1200, Pittsburgh, PA 15224, United States of America. Tel: 412-692-6583; Fax: 412-692-6472; E-mail: madans2@upmc.edu
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Abstract

Objective

Efficient diagnosis of an underlying genetic aetiology in a patient with congenital heart disease is essential to optimising clinical care. Copy number variants are one aetiology of congenital heart disease; the majority are identifiable by targeted fluorescence in situ hybridisation or array comparative genomic hybridisation, not by classical cytogenetic analysis. This study assessed the utility of array comparative genomic hybridisation as a first-tier diagnostic test for neonates with congenital heart disease.

Study design

A prospective chart review of neonates with congenital heart disease in the Cardiac Intensive Care Unit at Children’s Hospital of Pittsburgh of UPMC was performed. Patients were tested by array comparative genomic hybridisation and classical cytogenetic analysis simultaneously. Data collected included all chromosome abnormalities detected, physical examination findings, and imaging results. McNemar’s test was used to compare detection of array comparative genomic hybridisation and classical cytogenetic analysis.

Results

Of 45 patients, three (6.7%) had an abnormality detected by classical cytogenetic analysis and an additional 10 (22.2%) had a copy number variant detected by array comparative genomic hybridisation, highlighting an increased detection rate (p=0.008). Several of these copy number variants had unclear clinical significance, requiring additional investigation. The prevalence of dysmorphology and/or comorbidity in this population was 72%. Identification of dysmorphic features was greater when assessed by a geneticist than by providers of different subspecialties.

Conclusions

Array comparative genomic hybridisation has significant clinical utility as a first-tier test in this population, but it carries the potential for incidental findings and results of uncertain clinical significance. Collaboration between cardiologists and medical geneticists is essential to providing optimal clinical care.

Keywords

Congenital heart defectchromosome abnormalities

Information

Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Issue 1 , January 2015 , pp. 115 - 122
Copyright
Copyright © Cambridge University Press 2013 

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