| Objectives: To investigate the best detecting time in different types of CNS malformations and explore the research value of ultrasound combined with genetic detection in phenotype-genotype of CNS malformed children.To provide genetic testing ideas for prenatal diagnosis of CNS malformations.Methods: 18790 Pregnant woman were collected retrospectively from June 2016 to December 2018,126 among them were done karyotype analysis.(1)CNS malformed fetuses were statistical analyzed and follow-up which include of detected gestational weeks,types of deformities,number of deformities and affected sites.(2)Based on the results of ultrasound screening,pregnant women undergoing karyotype analysis were divided into three groups:(1)CNS deformity group: CNS malformed fetus;(2)Control group 1: fetal whose CNS was normal but has other system structure or soft indicators were abnormal;(3)Control group 2: fetal whose structure or soft indicators were normal but at high risk of chromosomal abnormalities.Chi-square test was used to analyze the incidence of karyotype abnormalities among different groups.(3)CMA was done in normal cases of chromosome karyotype analysis at the CNS malformations group and combination with the results of karyotype analysis,the phenotype-genotype correlation of CNS malformations was analyzed.(4)According to the number of malformations,CNS malformations group was classified into single malformation and multiple malformations;According to development of neural tube,CNS malformations group was classified into neural tube defects and brain dysplasia.Chi-square test was used to analyze the incidence of karyotype abnormalities among different groups.Results:1.83 CNS malformed fetuses were detected in 18790 cases,with a detection rate of4..42 ‰.15 types of deformities were involved,with spina bifida being the most common.Neural tube abnormalities and structural abnormalities in the middle brain were detected during the early and second trimester,while ventriculomegaly and hydrocephalus were often detected in the last trimester.There were 52 cases of single malformations and 31 cases of complex malformations in our dates,which the main associated malformations were circulatory system deformities,skeletal system deformities and facial deformities.2.Among 126 pregnant women who underwent chromosome karyotype analysis,30 cases of CNS malformations group,the detection rate of abnormal karyotype was33.3%(10/30)with 18-trisomy syndrome the most;36 cases of control group 1,the detection rate of abnormal karyotype was 30.6%(11/36)with 21-trisomy syndrome the most;36 control group 2,the detection rate of abnormal karyotype was 8.4%(5/60)with 21-trisomy syndrome the most.The incidence of karyotype abnormalities was significant differences among three groups(P < 0.05).Chi-Square Segmentation was used to pairwise comparison about incidence of karyotype abnormalities among three groups,there was no significant difference between CNS malformations group and control group 1(P > 0.125);There was significant difference between CNS malformations group and control group 2(P<0.125);There was significant difference between control group 1 and control group 2.3.A total of 20 fetuses of CNS malformations were detected by CMA.Two cases of pathogenic CNVs were detected and both of them involved pathogenic genes of CNS malformations(PDCD1,HDLBP,SHH).Through CMA detection,the detection rate of abnormal chromosomal in CNS malformed children has been increased by 6.7%(2/30).4.In the CNS malformations group,there were 11 cases of single malformation with27.3%(3/11)detection rate of abnormal chromosome and 19 cases of multiple malformations with 47.4%(9/19)detection rate of abnormal chromosome.There was no significant difference in abnormal chromosome detection rate between tow groups((P>0.05).There were 15 cases of neural tube malformations with 13.3%(2/15)detection rate of abnormal chromosome and 14 cases of brain dysplasia with 66.7%(10/15)detection rate of abnormal chromosome.There was significant difference in abnormal chromosome detection rate between tow groups((P<0.05).5.Neural tube defects and Dandy-walker deformity ware mainly 18-trisomy syndrome.HPE ware mainly 13-trisomy syndromes and MD.CNS minor deformities such as broadened ventricular system and choroid plexus cysts ware mainly 21-trisomy syndromes.Conclusions:1.Through systematic and standardized ultrasound scans,it is possible to make a more accurate assessment of the fetal CNS structure and its development.It can detect severe CNS malformations of the fetus in early time and reduce the harmful of poor pregnancy to mothers and infants.Neural tube defects are often detected during early pregnancy,spina bifida and abnormal brain middle structures are often detected during mid-pregnancy and hydrocephalus and cerebral hemorrhage are often detected during late pregnancy.2.CMA detection can improve the detection rate of chromosomal abnormalities in CNS malformation and it help to discover the causative genes of CNS malformations(PDCD1,HDLBP,SHH).3.CNS malformed children are often accompanied by chromosomal abnormalities but the risk of chromosomal abnormalities does not increase with the number of malformations.The risk of chromosomal abnormalities is related to the types of CNS malformations,and abnormal brain development is significantly higher than neural tube defects4.There are differences in ultrasound phenotypes between children with CNS deformities caused by different chromosomal abnormalities.In the prenatal ultrasound diagnosis,different types of CNS deformities combined malformations have certain direction for the diagnosis of chromosomal abnormalities. |
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