Prenatal Array Comparative Genomic Hybridization in Fetuses With Structural Cardiac Anomalies

Area of Science:

• Prenatal Genetics
• Genomic Medicine
• Fetal Medicine

Background:

• Fetal structural cardiac anomalies are a significant concern in prenatal diagnosis.
• Array comparative genomic hybridization (CGH) offers high resolution for detecting chromosomal abnormalities.
• Previous studies have explored array CGH for various fetal conditions, but its specific utility in cardiac anomalies requires further examination.

Purpose of the Study:

• To evaluate the diagnostic performance of array CGH in identifying fetal cardiac anomalies.
• To determine the proportion of pathogenic copy number variants (CNVs) associated with fetal cardiac anomalies.
• To assess the clinical utility and challenges of array CGH in prenatal genetic testing for cardiac defects.

Main Methods:

• Prospective recruitment of 22 pregnant women with diagnosed fetal structural cardiac anomalies.
• Exclusion of cases with normal rapid aneuploidy detection and FISH for 22q11.2 testing.
• Analysis of samples using array CGH.

Main Results:

• Array CGH identified pathogenic results in 14% of the prospectively recruited cases.
• Pathogenic copy number variants (CNVs) with variable expressivity and penetrance constituted a significant portion of positive findings.
• Identified CNVs included an 8p deletion (involving GATA4), a 16p11.2 duplication, and a 15q11.2 deletion.
• One case revealed an incidental finding of carrier status for a recessive disease.

Conclusions:

• Array CGH enhances the diagnostic yield in fetuses with cardiac anomalies.
• A notable proportion of positive array CGH results involved pathogenic CNVs, often linked to neurodevelopmental issues.
• The interpretation and counseling for certain CNVs in the prenatal setting remain challenging due to variable penetrance and expressivity.