Classifying and Evaluating Fetuses With Ventriculomegaly in Genetic Etiologic Studies

Abstract

The association between genetics and fetuses with ventriculomegaly (VM) is unknown. This study aimed to classify and evaluate abnormal copy number variations (CNVs) in fetuses with VM. From December 2016 to September 2020, amniotic fluid or umbilical cord blood from 293 pregnant women carrying fetuses with VM was extracted for single-nucleotide polymorphism microarray (SNP array). Among 293 fetuses with VM, 31 were detected with abnormal CNVs, including 22 with pathogenic CNVs (7.51%) and nine with variation of uncertain clinical significance (VUS) CNVs (3.07%). Of the 22 fetuses with pathogenic CNVs, 13 had known disease syndromes. Among the 293 fetuses, 133 had mild isolated VM [pathogenic CNVs, 7/133 (5.26%)]; 142 had mild non-isolated VM [pathogenic CNVs, 13/142 (9.15%)]; 12 had severe isolated VM [pathogenic CNVs, 2/12 (16.67%)]; and six had severe non-isolated VM (no abnormal CNVs was detected). There was no statistical significance in the rate of pathogenic CNVs among the four groups (P = 0.326, P > 0.05). Among the 267 fetuses with successful follow-up, 38 were terminated (of these, 21 had pathogenic CNVs). Of the 229 fetuses, two had developmental delay and the remaining 227 had a good prognosis after birth. Overall, the results are useful for the detection of fetal microdeletion/microduplication syndrome and for the accurate assessment of fetal prognosis in prenatal consultation.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly

“…With the development of molecular genetic technology, CMA has been gradually applied to detect these chromosomal submicroscopic imbalances due to higher resolution. For our VM cases, the detection rate of chromosomal abnormality using CMA was 16.5%, slightly lower than some studies reporting 17.9–20.6% ( 2 , 17 ) and higher than other studies reporting 6.2–16.3% ( 3 , 10 , 11 , 18 – 20 ). It has been reported that CMA could yield an additional detection rate as a first-tier diagnostic tool in VM, with an incremental yield ranging from 5 to 26% ( 1 , 8 ).…”

“…Chang et al ( 2 ) reported a 12.1% rate of chromosomal abnormalities in 281 fetuses with VM ( 2 ). Among the abnormal karyotypes in fetuses with VM, trisomy 21 was found to be the most common chromosomal aneuploidy ( 2 , 3 , 10 , 11 ), which was also observed in our VM cases. As known, chromosomal CNVs smaller than 5 Mb could hardly be identified by karyotyping.…”

“…In addition, CMA can not detect the balanced chromosomal translocations in case 164. Despite the fact that CMA was highly recommended for prenatal diagnosis of fetal VM ( 3 , 11 ), we currently recommend that it should be used in combination with karyotyping to provide more comprehensive genetic counseling.…”

“…In order to further delineate the correlation between CNVs and VM, we made a literature review on VM cases carrying LP/P CNVs excluding common aneuploidies ( 2 , 3 , 7 , 10 – 12 , 16 – 20 , 24 , 26 – 28 ). A total of 231 LP/P CNVs in published VM cohort studies were collected.…”

“…Fetal ventriculomegaly (VM), defined as an atrial diameter of ≥10 mm, is one of the most common central nervous system (CNS) abnormalities observed during pregnancy. As a soft marker in prenatal ultrasound findings, the incidence rate of fetal VM is 0.03-2.20% (1)(2)(3). According to the suggestions from Society for Maternal-Fetal Medicine (SMFM), fetal VM could be typically classified into two categories: mild (10-15 mm) or severe (>15 mm) or mild (10-12 mm), moderate (13-15 mm) or severe (>15 mm) (4).…”