| ObjectiveTo analyze the relationship between different types of fetal ventriculomegaly(VM)and copy number variants(CNVs),compare the diagnostic utility between karyotype analysis and chromosomal microarray analysis(CMA)in fetuses with VM and investigate the genetic etiology and pregnancy outcomes of fetal VM.MethodsA total of 232 cases of fetuses with VM that underwent invasive prenatal diagnosis in the Department of Obstetrics and Gynecology of Nanfang Hospital affiliated to Southern Medical University from 2014 to 2019 were collected.The chromosomal karyotype analysis and genome-wide CMA test results of these fetuses with VM were systematically analyzed.SPSS 20.0 software was used for statistical analysis and chi-square test was used to compare the abnormal detection rates between karyotype analysis and CMA in different types of fetal VM.Pregnancy outcomes and postnatal development were followed by medical records or telephone.Results(1)The abnormal detection rate of karyotype analysis was 14.2%(33/232),and the rate of chromosomal abnormalities in fetuses with non-isolated VM was higher than that in fetuses with isolated VM(17.6%vs.7.6%),the difference was statistically significant(x2=4.315,P=0.038).(2)The detection rate of CMA was 20.7%(36/174),8.6%(15/174)of which were pathogenic CNVs,9.2%(16/174)were benign CNVs,and 2.9%(5/174)were variants of uncertain significance.The positive rate of CNVs in fetuses with non-isolated VM was higher than that in fetuses with isolated VM(26.3%vs.10.0%),and the difference was statistically significant(χ2=6.377,P=0.012)(3)Comparison of detection rates:In the non-isolated VM group,the detection rate of CNVs by CMA was 26.3%(30/114),while the abnormal detection rate of karyotype analysis was 14.0%(16/114),with statistically significant difference(χ2=5.338,P=0.021).In the isolated VM group,the detection rate between the two was of no statistical difference(P>0.05).Of the 153 cases of fetal VM with normal karyotype,21 cases were detected with CNVs by CMA,with an additional detection rate of 13.7%(21/153),and the additional detection rate of pathogenic CNVs was 1.3%(2/153).When the fetal VM was combined with other neurological abnormalities,the additional detection rate of CMA was 20.8%(11/53),higher than that in fetel VM with other systematic abnormalities(9.1%～16.7%)(4)The pathogenic CNVs detected by CMA in fetal VM comprised several pathogenic genes such as KIF7,DNAH5,DLL1 and TBP.The related microdeletion or microduplication syndromes included:15q26 overgrowth syndrome,Cri-du-Chat syndrome,2q37 monosomy syndrome and 16p13.11 microdeletion syndrome,which were associated with neurodevelopmental disorders.(5)Pregnancy outcomes and development follow-up:among 174 fetuses with VM detected by CMA,46 fetuses were terminated,17 were lost to follow-up,three died soon after birth.Thirteen in fifteen cases of fetal VM detected with pathogenic CNVs were terminated.Four cases of fetal VM with normal karyotype but detected with benign or ambiguous CNVs developed different degrees of motor,language and mental retardation after birth(from seven months to more than five years old),among which three cases were prenatally diagnosed with isolated VM and normal karyotype.Conclusions(1)Fetuses with VM founded by prenatally examination increased the risk of chromosomal abnormalities and CNVs,especially the non-isolated VM fetuses merged with neurological abnormalities,suggesting karyotype analysis combined with CMA detection(2)Compared with conventional karyotype analysis,CMA can effectively improve the abnormal detection rates in fetuses with VM,with a pathogenic CNVs detection rate of 8.6%and an additional detection rate of 13.7%in the fetal VM with normal karyotype.(3)The discovery of pathogenic CNVs affected the pregnancy outcomes of fetuses with VM.(4)Fetuses with isolated VM detected with normal karyotype but CNVs were at risk of neurodevelopmental delay after birth,thus regular follow-up was required. |
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