背景:丹迪-沃克综合征(DWS)是一种罕见的先天性中枢神经系统(CNS)畸形,表现为小脑疣发育不足或发育不良,第四脑室和后颅窝大池扩张。发病率约为1/25000-1/35000。目前,DWS的病因和发病机制尚不完全清楚。它通常被认为是一种与遗传因素和环境因素有关的多因素遗传疾病。到目前为止,还没有对DWS染色体谱进行大样本量分析。本研究旨在通过总结Dandy-Walker综合征的临床特点及妊娠结局,为产前诊断提供临床参考。
方法:对19,506例孕妇中的76例胎儿Dandy-Walker综合征进行了基因检测。快速产前核型分析,单核苷酸多态性阵列(SNP-array)和BACs-on-Beads™(BoB)用于产前遗传诊断.超声检查结果,记录遗传分析和妊娠结局.
结果:76例中,19个是孤立的DWS,57例伴有其他超声可见异常。最常观察到中枢神经系统的超声异常,由DWS陪同。76例中有25例染色体异常,高龄孕妇或合并其他超声异常的孕妇染色体异常率增加。在孤立的DWS组的19例中,九名孕妇选择终止妊娠,7例继续妊娠,所有婴儿均正常。在57例除胎儿DWS以外的病理超声表现的孕妇中,44选择终止妊娠,12例继续妊娠。进一步随访发现一名新生儿出生后神经发育迟缓。一名女性新生儿出现非常严重的感音神经性耳聋,婴儿出生后7天死亡,多器官发育异常。
结论:胎儿超声检查中的DWS孕妇应进行仔细而全面的胎儿超声扫描,并进行进一步的产前遗传检测,包括核型分析和SNP阵列。在孤立的DWS妊娠中,没有染色体畸变的胎儿的预后良好,而在非孤立的DWS妊娠中,胎儿的预后较差。
BACKGROUND: Dandy-Walker syndrome (DWS) is a rare congenital malformation of the central nervous system (CNS), characterized by underdevelopment or dysplasia of the cerebellar vermis, expansion of the fourth ventricle and posterior fossa cistern. The incidence is aboutapproximately 1/25000-1/35000. At present, the etiology and pathogenesis of DWS are not completely clear. It is mostly considered to be a multifactorial genetic disease that is related to both genetic factors and environmental factors. There is no large sample size analysis of the chromosomal profile of DWS up to now. This study aims to provide clinical reference for prenatal diagnosis via summarizing the clinical features and pregnancy outcomes of Dandy-Walker syndrome.
METHODS: A total of 76 cases of foetal Dandy-Walker syndrome out of 19,506 pregnant women underwent cordocentesis or amniocentesis for genetic detection. Rapid prenatal karyotyping, single nucleotide polymorphism array (SNP-array) and BACs-on-Beads™ (BoBs) were performed for prenatal genetic diagnosis. The results of ultrasonography, genetic analysis and pregnancy outcome were recorded.
RESULTS: Of the 76 cases, 19 were isolated DWS, while 57 cases were accompanied by other ultrasound-visible abnormalities. Ultrasound abnormalities of the CNS were most frequently observed, accompanied by DWS. Twenty-five out of 76 cases had chromosomal abnormalities, and the rate of chromosomal abnormalities increased in pregnant women of advanced maternal age or in combination with other ultrasound abnormalities. Of the 19 cases in the isolated DWS group, nine pregnant women chose to terminate the pregnancy, while seven cases continued the pregnancy and all infants were normal. Among the 57 pregnant women with pathological ultrasound manifestations other than foetal DWS, 44 chose to terminate the pregnancy, while 12 cases continued the pregnancy. Further follow-up revealed one newborn with postnatal neurodevelopmental delay. A female term neonate presented with very severe sensorineural deafness, and an infant died 7 days after birth with abnormal development of multiple organs.
CONCLUSIONS: Pregnant women with DWS in foetal ultrasonic examination should be offered a careful and comprehensive foetal ultrasound scan and further prenatal genetic testing including karyotype analysis and SNP-array. The prognosis of the foetus without chromosomal aberration is good in isolated DWS pregnancies but poor in nonisolated DWS pregnancies.