A Chinese multicenter retrospective study of isolated increased nuchal translucency associated chromosome anomaly and prenatal diagnostic suggestions

Abstract

Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). On top of that, these limited number of researches were all designed as single-arm studies and the control group was missing. In this study, we conducted a multicenter, retrospective study using amniotic fluid samples collected from 1197 pregnant women having fetuses with isolated increased NT (INT group) or normal NT values (NNT group). Copy number variation sequencing (CNV-seq) was performed to determine their chromosome status and pathogenic variations were validated using SNP array. Overall, 59 chromosome aneuploidies, 34 pathogenic CNVs and 23 copy number variants of unknown significance (VOUS CNVs) were discovered. the INT group had a significantly higher proportion of aneuploidy (19.44%) and pathogenic CNV (8.33%) than the control group (3.49% and 2.30% respectively), and 88.89% of the pathogenic CNVs were related to heart defects. Additionally, more male fetuses were presented in the INT group (68.51%), but they did not have a higher risk (Relative Risk = 1.03) of carrying pathogenic chromosome variations than female fetuses. Our results demonstrated that fetuses with isolated increased NT had a distinct pattern of chromosome abnormality and majority of detected pathogenic CNVs could be linked to the congenital heart disease. Furthermore, because a considerable proportion of pathogenic CNVs were detected, we strongly recommend to perform a joint test of karyotyping and CNV analysis in prenatal diagnosis for fetuses with isolated increased NT in order to decrease the incident of missed diagnosis.

Application of chromosome microarray analysis and karyotyping in diagnostic assessment of abnormal Down syndrome screening results

“…The positive rate was lower than previous reports because the NT cut-off for invasive testing in our department is 2.5 mm vs. 3.0-3.5 mm in most previous studies. Consist with these studies, aneuploidy and gross deletion/duplication accounted for more than 80% chromosomal abnormalities (NT cut-off 2.5 ~ 3.0 mm: 80% ~ 90%, NT cut-off 3.5 mm: > 90%) [16][17][18][19][20][21]. CMA could detect 1.9% more CNVs than karyotyping in serum screening group, which is consistent with previous reports [22,23].…”

Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study

“…Karl Oliver Kagan et al demonstrated that the prevalence of abnormal karyotype was 19.2% and the trisomy 21 (68.34%) was the most common chromosome anomaly, followed by trisomy 18 (21.11%) and trisomy 13 (10.55%) [17,18]. Jin Hua et al also reported recently that the incidence of chromosome abnormality was 28.7% in increased NT group while only 7.81% was found in normal group [19]. In our study, 19.51% chromosomal abnormalities were detected by karyotype, and trisomy 21 (60.00%) was the most common, followed by trisomy 18 (12.50%), and trisomy 13 (5.00%), which was consistent with the above literature reports.…”

Prenatal diagnosis of Noonan syndrome in a set of monozygotic twins- a case report

“…NT is the thickness of fluid collection in the fetal neck, which can be observed by an ultrasound scan between 11 and 13 + 6 weeks of gestation. Increased NT has been reported to be associated with chromosomal abnormalities and fetal structural defects [ 5 , 6 ]. CH can be clearly differentiated from a simple increase in NT.…”