Clinical Characteristics And Genetic Analysis Of 152 Cases Of Fetal Nervous System Malformation

OBJECTIVETo understand the types and ultrasonographic features of fetal nervous system malformations,and to analyze the incidence of chromosomal abnormalities in isolated fetal nervous system malformation and fetal nervous system malformations plus other ultrasound anomalies.METHODA total of 152 fetuses with nervous system malformations diagnosed by color ultrasound in the Women’s and Children’s Hospital affiliated to Xiamen University from January 2017 to December 2019 were studied.After genetic counseling,interventional prenatal diagnosis of fetal chromosome karyotype and/or SNP array test were performed before the induced labor,and fetal autopsy was performed after the induced labor.According to the presence or absence of extra-nervous system malformations,the subjects were divided into two groups:simple nervous system malformation group(n=86)and nervous system with external malformations group(n=66).The ultrasonographic features and types,chromosome karyotype,and SNP array results of fetal nervous system malformations were analyzed retrospectively.RESULT1.Fetal nervous system malformations have definite ultrasonographic features,which can be divided into two categories:neural tube malformation and brain structural dysplasia,the former includes exencephaly-anencephaly,spina bifida,meningocele、cephalocele and hydrocephalus,and the latter includes agenesis of corpus callosum,Dandy-Walker malformation,holoprosencephaly and brain dysplasia.4 cases of brain dysplasia with suspected abnormal development of cerebral gyrus and sulcus were diagnosed by prenatal magnetic resonance imaging(MRI).2.Among fetal nervous system malformations,the incidence of holoprosencephaly was the highest(28.28%),followed by agenesis of corpus callosum(19.08%).Among the simple nervous system malformations,there were 74 cases of single nervous system malformations(48.68%),12 cases of multiple nervous system malformations(7.89%),and 66 cases of fetal nervous system malformations plus other anomalies(43.42%).In the fetal nervous system malformations plus other anomalies group,the frequency of holoprosencephaly malformation was the highest,up to 20 cases(90.91%).Nervous system malformations with other system malformations include skeletal system malformations、facial abnormalities、congenital heart disease、digestive system malformations、urinary system malformations、fetal edema、lymphatic cysts.3 The diagnostic results of prenatal ultrasound and fetal autopsy after the induced labor were consistent,and the coincidence rate was 100%.Among them,6 cases of fetal structural abnormalities and fetal abnormal syndrome were found by autopsy after the induced labor,including 1 case of amniotic band syndrome,2 cases of omphaloceleexstrophy-imperforate anus-spinal defects,1 case of VATER syndrome,and 1 case of body stalk anomaly.4.In the nervous system malformations,the proportion of fetal chromosome abnormalities was higher,and the detection rate of abnormal chromosome karyotype was 20.27%.Among all kinds of nervous system malformations,the detection rate of chromosome abnormalities in fetuses with holoprosencephaly is the highest,which is as high as 63.63%.The main abnormal karyotype is trisomy 13 syndrome.5.Comparative analysis showed that the rate of chromosome abnormality in the group of fetal nervous system malformations plus other anomalies group was significantly higher than that in the isolated nervous system malformation group(40.63%vs 4.76%),χ2=26.73,P<0.001.6.SNP array technique showed that 2 cases of normal karyotype were pathogenic chromosome copy number variation,and 1 case of fetal nervous system malformation and intrauterine stillbirth showed 18-trisomy by chromosome microarray analysis.COUNLUSION1.Ultrasound technology is widely used in the examination of fetal nervous system malformations,and most of these abnormalities can be detected efficiently.Prenatal MRI plays a better role in the supplement and diagnosis of brain dysplasia and agenesis of corpus callosum.2.Among the fetal nervous system malformations,the incidence of exencephalyanencephaly was the highest,followed by agenesis of corpus callosum.The most common fetal nervous system malformations plus other anomalies is holoprosencephaly.Among other malformations,skeletal system deformities,facial abnormalities and congenital heart diseases are common.3.Postpartum fetal autopsy not only helps to confirm prenatal ultrasound diagnosis,but also can identify the syndrome that can not be diagnosed by ultrasound under the condition of small gestational weeks and other factors.4.There is a high proportion of chromosomal abnormalities in nervous system malformations,especially brain structural dysplasia are related to chromosomal aneuploidy abnormalities.5.Compared with isolated nervous system malformations group,the rate of chromosome abnormalities in fetal nervous system malformations plus other anomalies group was higher.6.Chromosome microarray analysis can detect microdeletions and microduplications syndrome,improve the detection rate of chromosome abnormalities and have the advantage of obtaining chromosome detection without cell culture.