Meckel-Gruber综合征的产前诊断学特征及文献复习

Prenatal diagnostic characteristics and literature review of Meckel-Gruber syndrome

目的探讨Meckel-Gruber综合征(MKS)的产前诊断学特征。方法回顾性分析2019年7月5日于湖北省妇幼保健院超声诊断科经产前超声诊断的一例早孕期MKS胎儿的超声影像特征、病理结果及基因检测结果,并复习文献。结果孕妇28岁,初产妇,孕11^(+6)周,产前超声图像表现为胎儿颅骨环回声中断,脑膜与脑组织膨出;双肾体积增大伴有细小无回声和小囊肿;双手、双足轴后型多指/趾,诊断为MKS。病理结果显示该胎儿脑膨出,轴后型多指/趾,肾髓质囊性病变及单纯腭裂。全外显子组测序发现,该胎儿携带两个新的CC2D2A基因杂合突变:c.3688 C>T(p.Arg1230^(*))和c.4314+1-4314+2insT。Sanger测序显示,该两个突变分别遗传自父亲和母亲,为复合杂合突变。该两个基因突变位点均为首次报道,根据美国医学遗传学与基因组学学会(ACMG)变异分类标准与指南,这两个突变位点为疑似致病性突变(PVS1+PM2)。结论MKS在早孕期多表现为脑膨出,肾脏体积增大伴有小的囊性病变与轴后型多指/趾。早孕期是产前诊断MKS的最佳时期,高通量测序技术提供了MKS重要的遗传学信息。

Objective To investigate the diagnostic features of Meckel-Gruber syndrome(MKS).MethodsThe ultrasonographic data,pathological findings and genetic testing results of a fetus with MKS diagnosed prenatally in Department of Ultrasonography,Maternal and Child Health Hospital of Hubei Province on July 5,2019 were analyzed retrospectively,and the relevant literatures were reviewed.ResultsA 28-year-old healthy Chinese woman presented at the 11^(+6)weeks of gestation underwent the first-trimester ultrasound investigation.The ultrasound examination showed interruption of fetal skull hyperechoic ring with protrusion of meninges and cerebral tissue around occipital region,enlarged kidneys with small anechoic and cysts,postaxial polydactyly of double hands and double feet in this fetus,diagnosed as MKS.The pathological examination of the aborted fetus showed occipital encephalocele,postaxial polydactyly,polycystic kidneys and cleft palate.By whole-exome sequencing,two novel heterozygous mutations[c.3688 C>T(p.Arg1230^(*)),c.4314+1-4314+2insT]in the CC2D2A gene were identified.These two mutations had never been described before.Sanger sequencing validated the mutations in the fetus and revealed that they were originated from the father and mother,respectively.These two variants were classified as likely pathogenic mutations(PVS1+PM2)according to the variation classification criteria and guidelines of American College of Medical Genetics and Genomics(ACMG).ConclusionsIn early pregnancy,MKS is mostly characterized by occipital encephalocele,enlarged kidneys with small pyramidal cysts and postaxial polydactyly.The first trimester of the pregnancy is the earliest and best time for prenatal diagnosis of MKS.High throughput sequencing technology provides important genetic information for the family with fetuses affected by MKS.