Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with congenital gastrointestinal obstruction

Background Congenital gastrointestinal obstruction (CGIO) mainly refers to the stenosis or atresia of any part from the esophagus to the anus and is one of the most common surgical causes in the neonatal period. The concept of genetic factors as an etiology of CGIO has been accepted, but investigations about CGIO have mainly focused on aneuploidy, and the focus has been on duodenal obstruction. The objective of this study was to evaluate the risk of chromosome aberrations (including numeric and structural aberrations) in different types of CGIO. A second objective was to assess the risk of abnormal CNVs detected by copy number variation sequencing (CNV-seq) in fetuses with different types of CGIO. Methods Data from pregnancies referred for invasive testing and CNV-seq due to sonographic diagnosis of fetal CGIO from 2015 to 2020 were obtained retrospectively from the computerized database. The rates of chromosome aberrations and abnormal CNV-seq findings for isolated CGIOs and complicated CGIOs and different types of CGIOs were calculated. Results Of the 240 fetuses with CGIO that underwent karyotyping, the detection rate of karyotype abnormalities in complicated CGIO was significantly higher than that of the isolated group (33.8% vs. 10.8%, p < 0.01). Ninety-three cases with normal karyotypes further underwent CNV-seq, and CNV-seq revealed an incremental diagnostic value of 9.7% over conventional karyotyping. In addition, the incremental diagnostic yield of CNV-seq analysis in complicated CGIOs (20%) was higher than that in isolated CGIOs (4.8%), and the highest prevalence of pathogenic CNVs/likely pathogenic CNVs was found in the duodenal stenosis/atresia group (17.5%), followed by the anorectal malformation group (15.4%). The 13q deletion, 10q26 deletion, 4q24 deletion, and 2p24 might be additional genetic etiologies of duodenal stenosis/atresia. Conclusions The risk of pathogenic chromosomal abnormalities and CNVs increased in the complicated CGIO group compared to that in the isolated CGIO group, especially when fetuses presented duodenal obstruction (DO) and anorectal malformation. CNV-seq was recommended to detect submicroscopic chromosomal aberrations for DO and anorectal malformation when the karyotype was normal. The relationship between genotypes and phenotypes needs to be explored in the future to facilitate prenatal diagnosis of fetal CGIO and yield new clues into their etiologies.

Automated summary

This study aimed to evaluate the risk of chromosomal aberrations and copy number variations (CNVs) in different types of congenital gastrointestinal obstruction (CGIO) and explore the genetic etiology of CGIO using CNV-seq. It was found that the risk of pathogenic chromosomal abnormalities and CNVs increased in the complicated CGIO group, especially in cases of duodenal obstruction (DO) and anorectal malformation. CNV-seq was recommended for detecting submicroscopic chromosomal aberrations when the karyotype was normal.