J Genet Med.  2020 Jun;17(1):21-26. 10.5734/JGM.2020.17.1.21.

Clinical application of chromosomal microarray for pathogenic genomic imbalance in fetuses with increased nuchal translucency but normal karyotype

• Lee D
• Go S
• Na S
• Park S
• Ma J
• Hwang D

• KMID: 2503607
• DOI: http://doi.org/10.5734/JGM.2020.17.1.21

Abstract

Purpose
To evaluate the additive value of prenatal chromosomal microarray analysis (CMA) in assessing increased nuchal translucency (NT) (≥3.5 mm) with normal karyotype and the possibility of detecting clinically significant genomic imbalance, based on specific indications.
Materials and Methods
Invasive samples from 494 pregnancies with NT ≥3.5 mm, obtained from the Research Center of Fertility & Genetics of Hamchoon Women’s Clinic between January 2019 and February 2020, were included in this study and CMA was performed in addition to a standard karyotype.
Results
In total, 494 cases were subjected to both karyotype and CMA analyses. Among these, 199 cases of aneuploidy were excluded. CMA was performed on the remaining 295 cases (59.7%), which showed normal (231/295, 78.3%) or non-significant copy number variation (CNV), such as benign CNV or variants of uncertain clinical significance likely benign (53/295, 18.0%). Clinically significant CNVs were detected in 11 cases (11/295, 3.7%).
Conclusion
Prenatal CMA resulted in a 3% to 4% higher CNV diagnosis rate in fetuses exhibiting increased NT (≥3.5 mm) without other ultrasound detected anomalies and normal karyotype. Therefore, we suggest using high resolution, non- targeting CMA to provide valuable additional information for prenatal diagnosis. Further, we recommend that a genetics specialist should be consulted to interpret the information appropriately and provide counseling and follow-up services after prenatal CMA.

Keyword

Nuchal translucency measurement; Increased nuchal translucency (≥3.5 mm); Prenatal chromosomal microarray; Prenatal chromosomal microarray analysis