BACKGROUND AND PURPOSE:

• ACMG/ACOG recommend the use of microarrays in the setting of fetal anomalies to identify not only aneuploidies, but also copy number variants
• Xia et al. (Prenatal Diagnosis, 2018) examined chromosomal abnormalities and copy number variations (CNVs) in fetuses with congenital heart disease (CHD)

METHODS:

• Cohort study
• Participants
  • Fetal CHD detected by prenatal echocardiography
• Standard ultrasound done between 20 and 26 weeks, followed by fetal echo if cardiac anomaly detected
• Chromosomal analysis
  • Conventional G-banded cytogenetic analysis
  • Comparative microarray analysis was performed using Affymetrix CytoScan HD platform
• Invasive diagnostic testing
  • Amniocentesis between 18-24 weeks, with consent
  • Cordocentesis performed if after 24 weeks
• Simple CHD
  • Single ASD (type II)
    • Atrioventricular septal defects were excluded
  • VSD
• Complex CHD
  • ≥2 congenital cardiovascular anomalies
  • Conotruncal defects
  • Aortic defects
  • Other defects (e.g., hypoplastic left heart syndrome)

RESULTS:

• 110 fetuses included in this study (87 with simple CHD)
• Conventional G-banding: Clinically significant chromosomal abnormalities were identified in 7.3% of fetuses
  • Chromosomal aneuploidies
    • 2 cases with trisomy 21
    • 2 cases with trisomy 18
    • 1 case with trisomy 13
    • 1 unusual case of mosaic trisomy 21
  • Chromosomal structural changes
    • 1 pericentric inversion
    • 1 deletion
  • 2 balanced translocations (likely benign)
    • Not picked up by microarray)
  • Microarray: Identified additional pathogenic variants in 15.5% (n=17) of the cohort
    • 13 CNVs were known to be associated with CHD
    • 10 cases (8.2%) had CNVs related to well-known syndromes, including 22q deletion syndrome (n=4)
    • Complex CHD was much more likely to have a finding on microarray (26.5%) vs simple CHD (3.7%)
    • 1% of cases had no abnormalities on microarray
    • 6 fetuses had VUS and some of these cases still went on to termination
  • 10 genes were identified as likely novel CHD candidate genes through gene functional enrichment analysis
    • More research is necessary to determine if these genes are causative

CONCLUSION:

• The authors found approximately 21% of fetuses with CHD had clinically significant results using microarray
• Microarray is not only reliable and necessary technique to identify chromosomal pathology in the setting of CHD, but also may help find additional genes underlying congenital cardiac disease

Learn More – Primary Sources:

Clinical application of chromosomal microarray analysis for the prenatal diagnosis of chromosomal abnormalities and copy number variations in fetuses with congenital heart disease

Related ObG Topics:

Microarrays and Microdeletions: Key Concepts Summarized

The Use of Microarrays in the Prenatal and Postnatal Setting – Current Professional Guidelines

Should Amniocentesis or Chorionic Villus Sampling Be Offered to All Pregnant Women?

Is Prenatal Microarray Use Justified as a First Tier Test for Fetal Congenital Heart Disease?