Cheng Dan, Shang Xiang, Gao Wanli, Barkhof Frederik, Liu Yaou
From the Departments of Radiology (D.C., Y.L.), and Obstetrics (X.S., W.G.), Beijing Tiantan Hospital, Capital Medical University, China; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, United Kingdom; and Department of Radiology and Nuclear Medicine (F.B.), Amsterdam University Medical Centers, the Netherlands.
Neurology. 2021 Nov 23;97(21):986-988. doi: 10.1212/WNL.0000000000012852. Epub 2021 Sep 23.
To identify fetal familial cerebral cavernous malformation (CCM) and a novel variation.
A 37-year-old pregnant woman (G4P0) presented with right-handed numbness since 2 weeks at 31 weeks of gestation. Evaluation with brain MRI revealed multiple CCMs. As a result, fetal MRI, fetal whole exome sequencing, and maternal Sanger sequencing were performed.
The mother's brain MRI demonstrated numerous CCMs involving the brain stem, cerebral hemispheres, and cerebellum. Fetal MRI showed a CCM located in the left frontal lobe in susceptibility-weighted imaging (SWI). The neuroimaging characteristics of the mother and the fetus suggested that their CCMs may be familial. Genetic analysis revealed a novel variation in (c.1A>G, p.0?), also called , in the mother and the baby. The mother delivered a daughter at 32 weeks of gestation with an Apgar score of 10 by cesarean section.
This variation of the initial codon in the gene leads to a phenotype with an early-onset. To our knowledge, this is the first-ever reported case of fetal familial CCM and this novel variation. Brain MRI has excellent sensitivity and specificity, providing the best option for detecting CCMs, even in utero, primarily when SWI is used.
识别胎儿家族性脑海绵状血管畸形（CCM）及一种新变异。
一名37岁孕妇（孕4产0），妊娠31周时自2周起出现右手麻木。脑部MRI评估显示多发CCM。因此，进行了胎儿MRI、胎儿全外显子组测序及母亲的桑格测序。
母亲的脑部MRI显示脑干、大脑半球及小脑有大量CCM。胎儿MRI在磁敏感加权成像（SWI）中显示左额叶有一个CCM。母亲和胎儿的神经影像学特征提示其CCM可能为家族性。基因分析在母亲和婴儿中发现了 （c.1A>G，p.0?）中的一种新变异，也称为 。母亲在妊娠32周时剖宫产分娩一女，阿氏评分10分。
基因起始密码子的这种变异导致早发型表型。据我们所知，这是首例报道的胎儿家族性CCM及这种新变异。脑部MRI具有出色的敏感性和特异性，为检测CCM提供了最佳选择，即使在子宫内，主要是使用SWI时。
