Korean Circ J.  2018 Mar;48(3):209-216. 10.4070/kcj.2017.0166.

Array Comparative Genomic Hybridization as the First-line Investigation for Neonates with Congenital Heart Disease: Experience in a Single Tertiary Center

• Choi BG
• Hwang SK
• Kwon JE
• Kim YH

• KMID: 2406924
• DOI: http://doi.org/10.4070/kcj.2017.0166

Abstract

BACKGROUND AND OBJECTIVES
The purpose of the present study was to investigate the advantages and disadvantages of verifying genetic abnormalities using array comparative genomic hybridization (a-CGH) immediately after diagnosis of congenital heart disease (CHD).
METHODS
Among neonates under the age of 28 days who underwent echocardiography from January 1, 2014 to April 30, 2016, neonates whose chromosomal and genomic abnormalities were tested using a-CGH in cases of an abnormal finding on echocardiography were enrolled.
RESULTS
Of the 166 patients diagnosed with CHD, 81 underwent a-CGH and 11 patients (11/81, 13.5%) had abnormal findings on a-CGH. 22q11.2 deletion syndrome was the most common (4/11, 36.4%). On the first a-CGH, 4 patients were negative (4/81, 5%). Three of them were finally diagnosed with Williams syndrome using fluorescent in situ hybridization (FISH), 1 patient was diagnosed with Noonan syndrome through exome sequencing. All of them exhibited diffuse pulmonary artery branch hypoplasia, as well as increased velocity of blood flow, on repeated echocardiography. Five patients started rehabilitation therapy at mean 6 months old age in outpatient clinics and epilepsy was diagnosed in 2 patients. Parents of 2 patients (22q11.2 deletion syndrome and Patau syndrome) refused treatment due to the anticipated prognosis.
CONCLUSIONS
Screening tests for genetic abnormalities using a-CGH in neonates with CHD has the advantage of early diagnosis of genetic abnormality during the neonatal period in which there is no obvious symptom of genetic abnormality. However, there are disadvantages that some genetic abnormalities cannot be identified on a-CGH.

Keyword

Array comparative genomic hybridization; Heart defects, congenital; Neonate

MeSH Terms

Ambulatory Care Facilities
Comparative Genomic Hybridization*
Diagnosis
DiGeorge Syndrome
Early Diagnosis
Echocardiography
Epilepsy
Exome
Heart Defects, Congenital*
Humans
In Situ Hybridization, Fluorescence
Infant, Newborn*
Mass Screening
Noonan Syndrome
Parents
Prognosis
Pulmonary Artery
Rehabilitation
Williams Syndrome

Figure

• 

  Figure 1 a-CGH copy number profiles of constitutional DNA samples from the normal control and syndromic DNA samples from the patient with DiGeorge syndrome. a-CGH results from normal control (A) and DiGeorge syndrome (B) DNA analysis. The X-axis represents the chromosomes, while the Y-axis represents the log2 patient/healthy control fluorescence intensity ratios (thresholds −1 [loss] and +1 [gain]) for each chromosome, respectively. a-CGH results from constitutional DNAs (A) revealed gains and losses of small chromosomal regions. a-CGH results from DiGeorge syndrome DNAs (B) revealed significant losses of chromosome 22. a-CGH = array comparative genomic hybridization.

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