Zhang Hongyun, Linpeng Siyuan, Teng Yanling, Peng Can, Liang Desheng, Li Zhuo, Wu Lingqian
Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Department of Genetics and Eugenics, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University, Changsha, China.
Front Pediatr. 2023 Aug 1;11:1177137. doi: 10.3389/fped.2023.1177137. eCollection 2023.
The prenatal prevalence of isolated ventriculomegaly is 0.039%-0.087%. Most isolated mild ventriculomegaly (MV) fetuses (>90%) have a favorable prognosis. However, 5.6% to 7.9% of fetuses with isolated MV have adverse neurodevelopmental outcomes. In this study, we reported the first case of prenatal Snijders Blok-Fisher syndrome (OMIM: #618604) caused by a truncating variant of (OMIM: 602480) in a fetus with transient isolated bilateral MV. The results of karyotype analysis, chromosomal microarray analysis, and TORCH infection evaluation for the fetus were all negative. However, a likely pathogenic nonsense variant of NM_006236.3 (): c.640C > T [rs1254251078] p.(Q214) was identified by whole-exome sequencing (WES). Despite sufficient genetic counseling, the mother refused to undertake further brain magnetic resonance imaging (MRI) and decided to keep the fetus. She gave birth to a male infant through a full-term vaginal delivery. With a long-term follow-up, the infant unfortunately gradually presented with delayed motor development. The postnatal brain MRI of the proband showed dysplasia of the corpus callosum and ventriculomegaly. Considering the high probability of misdiagnosis for such cases, we further summarized the prenatal phenotypes from 19 reported patients with variants in The results revealed that 14 patients displayed a normal prenatal ultrasonographic manifestation, while only approximately 26.32% of fetuses showed MV or cysts without structural deformity. Thus our findings expand the variant spectrum of and suggest the importance of undertaking WES and brain MRI when the fetus has isolated bilateral MV.
孤立性脑室扩大的产前患病率为0.039% - 0.087%。大多数孤立性轻度脑室扩大（MV）胎儿（>90%）预后良好。然而，5.6%至7.9%的孤立性MV胎儿有不良神经发育结局。在本研究中，我们报告了首例产前诊断为斯奈德·布洛克 - 费舍尔综合征（OMIM：#618604）的病例，该病例由（OMIM：602480）的截短变异导致，胎儿有短暂的孤立性双侧MV。胎儿的核型分析、染色体微阵列分析和TORCH感染评估结果均为阴性。然而，通过全外显子测序（WES）鉴定出NM_006236.3（）的一个可能致病的无义变异：c.640C>T [rs1254251078] p.(Q214)。尽管进行了充分的遗传咨询，母亲仍拒绝进一步进行脑磁共振成像（MRI）检查，并决定保留胎儿。她通过足月阴道分娩产下一名男婴。经过长期随访，不幸的是，该婴儿逐渐出现运动发育迟缓。先证者出生后的脑MRI显示胼胝体发育不全和脑室扩大。考虑到此类病例误诊的可能性很高，我们进一步总结了19例报告的有变异患者的产前表型。结果显示，14例患者产前超声表现正常，而只有约26.32%的胎儿表现为MV或囊肿但无结构畸形。因此，我们的研究结果扩展了的变异谱，并提示当胎儿有孤立性双侧MV时，进行WES和脑MRI检查的重要性。
