Microarray analysis in fetuses with duodenal obstruction: It is not just trisomy 21

Abstract

Objective To explore the copy number variants (CNVs) in case of fetal duodenal obstruction (DO) and assess the associated prenatal findings and postnatal outcomes. Materials and methods This retrospective study reviewed 51 fetuses with DO and the findings of chromosomal microarray analysis (CMA) used as a first‐tier test in our institution between January 2014 and May 2019. Results The frequency of pathogenic aberrations in fetuses with DO was 15.7% (8/51), including 9.8% (5/51) pathogenic CNVs. Three fetuses with isolated DO each had a deletion on chromosome 13q, one fetus had duplication at 1q43q44, and one had microduplication at 17q12. No significant differences in pathogenic CNVs were observed between isolated DO and DO plus additional anomalies (4/42, 9.5% vs 1/9, 11.1%, P = .89). Of the 51 fetuses with DO, 11 pregnancies were terminated, and eight fetuses had chromosomal abnormalities; one pregnancy ended with intrauterine death, and there were 39 live births. Neonatal outcomes were available for 31 fetuses, and no neonatal deaths occurred after surgery. Conclusions Our cohort study demonstrated the value of CMA in fetuses with DO, suggesting that CNVs may underly genetic etiologies that should be considered in the diagnostic evaluation of DO. We think CMA should be recommended in case of DO.

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

“…The incremental diagnostic yield of CNV-seq in complicated CGIOs (20%) was higher than that in isolated CGIOs (4.8%), and the highest prevalence of pCNVs/likely pCNVs was found in the duodenal stenosis/atresia group (17.5%), followed by the anorectal malformation group (15.4%). These data were inconsistent with the reports by Bishop et al [ 13 ] in which a pathogenic microdeletion was found only in isolated duodenal atresia and by Zhang et al [ 15 ] in which no significant difference in pCNVs was observed between the isolated group and complicated group. However, we believe that the divergence might be due to the relatively low number of fetuses included in those studies.…”

“…The 13q deletion, resulting in Waardenburg syndrome type 4A (OMIM 277580), was the most frequently identified CNV in our study (cases 1 and 2). This finding was consistent with a finding in a previous study [ 15 ]. CNV-seq revealed a 9.76-MB deletion in 13q21.33q34 and an 8.99-MB deletion in 13q22.31q33.3.…”

“…Xia et al reported that the detection rates of pCNV and VOUS were 4.55% and 9.09% in digestive disorders, respectively [ 26 ]. In a recent study performed by Zhang et al [ 15 ], pCNVs were identified in 5 of 48 fetuses with DO at a detection rate of 10.4%. In our study, we observed different types of CGIO caused by stenosis or atresia.…”

“…Notably, abnormal migration of neural crest cells in conjunction with destruction of blood vessels may be the possible pathogenesis of duodenal atresia. Meanwhile, the relationship between 13q deletion and duodenal atresia has been described in several case reports [ 15 , 31 , 32 ]. In summary, we consider that haploinsufficiency of EDNRB might be a candidate gene to produce the phenotype of duodenal stenosis/atresia in a fetus with 13q deletion syndrome.…”

“…With the development of next-generation sequencing (NGS) technology, NGS-based copy number variation sequencing (CNV-seq) technology has gradually developed into a high-throughput, high-resolution, short turn-around time, and low-cost detection method [ 10 ], and it has been utilized in most prenatal diagnoses as a viable alternative methodology to CMA [ 11 , 12 ]. A few studies have shown that DO is also related to CNVs, such as 4q22.3 deletion [ 13 ] and 13q deletion [ 14 , 15 ]. Nevertheless, genetic investigations of CGIO have mainly focused on aneuploidy, and the focus has been on DO.…”