Prenatal genetic diagnosis of omphalocele by karyotyping, chromosomal microarray analysis and exome sequencing.

Objectives: The aim of this study is to share our experience in the prenatal diagnosis of omphalocele by karyotyping, chromosomal microarray analysis (CMA) and whole exome sequencing (WES).

Methods: In this retrospective study, 81 cases of omphalocele were identified from 2015 to 2020. Associated anomalies and prenatal diagnosis based on karyotyping, CMA and WES were analysed.

Results: Fifty-eight (71.6%) of the 81 foetuses had other ultrasound anomalies. Giant omphalocele was present in 11 cases (13.6%) and small omphalocele was present in 70 cases (86.4%). Chromosomal abnormalities were found in 24 foetuses (29.6%, 24/81), the most common of which were trisomy 18 (58.8%, 11/24) and trisomy 13 (29.2%, 7/24). Compared to isolated omphalocele, non-isolated omphalocele was accompanied by an increased prevalence of chromosomal abnormalities (4.3% (1/23) vs. 39.7% (23/58), χ² = 8.226, p = .004). All chromosomal abnormalities were found in small omphalocele. Aside from aneuploidy, CMA showed one pathogenic copy number variants (CNVs) for a detection rate of 1.2%, one variants of unknown significance (VOUS) and one instance of loss of heterozygosity (LOH). WES was performed on 3 non-isolated cases, and one was found to have pathogenic variants.

Conclusions: The most common genetic cause of omphalocele is aneuploidy and the prevalence of chromosomal abnormalities is increased with non-isolated and small omphalocele. CMA and WES can be useful for providing further genetic information to assist in prenatal counselling and pregnancy management.