University of Washington School of Medicine, Seattle, Washington, USA.
Department of Radiology, University of Washington School of Medicine, Seattle, Washington, USA.
Am J Med Genet A. 2021 Sep;185(9):2690-2718. doi: 10.1002/ajmg.a.61972. Epub 2020 Nov 18.
Twins have an increased risk for congenital malformations and disruptions, including defects in brain morphogenesis. We analyzed data on brain imaging, zygosity, sex, and fetal demise in 56 proband twins and 7 less affected co-twins with abnormal brain imaging and compared them to population-based data and to a literature series. We separated our series into malformations of cortical development (MCD, N = 39), cerebellar malformations without MCD (N = 13), and brain disruptions (N = 11). The MCD group included 37/39 (95%) with polymicrogyria (PMG), 8/39 (21%) with pia-ependymal clefts (schizencephaly), and 15/39 (38%) with periventricular nodular heterotopia (PNH) including 2 with PNH but not PMG. Cerebellar malformations were found in 19 individuals including 13 with a cerebellar malformation only and another 6 with cerebellar malformation and MCD. The pattern varied from diffuse cerebellar hypoplasia to classic Dandy-Walker malformation. Brain disruptions were seen in 11 individuals with hydranencephaly, porencephaly, or white matter loss without cysts. Our series included an expected statistically significant excess of monozygotic (MZ) twin pairs (22/41 MZ, 54%) compared to population data (482/1448 MZ, 33.3%; p = .0110), and an unexpected statistically significant excess of dizygotic (DZ) twins (19/41, 46%) compared to the literature cohort (1/46 DZ, 2%; p < .0001. Recurrent association with twin-twin transfusion syndrome, intrauterine growth retardation, and other prenatal factors support disruption of vascular perfusion as the most likely unifying cause.
双胞胎先天畸形和发育障碍的风险增加,包括脑形态发生缺陷。我们分析了 56 例先证者双胞胎和 7 例脑影像学异常的非严重孪生儿的脑影像学、同卵性、性别和胎儿死亡数据,并将其与基于人群的数据和文献系列进行比较。我们将我们的系列分为皮质发育畸形(MCD,N=39)、无 MCD 的小脑畸形(N=13)和脑破裂(N=11)。MCD 组包括 37/39(95%)的多微脑回(PMG)、8/39(21%)的软脑膜裂(脑裂畸形)和 15/39(38%)的脑室周围结节性异位(PNH),其中 2 例合并 PNH 但无 PMG。小脑畸形见于 19 人,其中 13 例仅小脑畸形,另 6 例小脑畸形合并 MCD。病变模式从弥漫性小脑发育不良到经典的 Dandy-Walker 畸形不等。脑破裂见于 11 例无脑积水、脑穿通畸形或无囊肿的白质丢失。我们的系列包括与人群数据相比,同卵(MZ)双胞胎(22/41 MZ,54%)显著增加(p=0.0110),与文献队列相比,双卵(DZ)双胞胎(19/41,46%)显著增加(p<0.0001)。与双胎输血综合征、宫内生长受限和其他产前因素的反复关联支持血管灌注中断是最可能的统一原因。