PDF(Pubmed)
Abstract：
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 POU3F3 (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 de novo likely pathogenic nonsense variant of NM_006236.3 (POU3F3): 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 POU3F3. 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 POU3F3 and suggest the importance of undertaking WES and brain MRI when the fetus has isolated bilateral MV.
摘要：
孤立性脑室增宽的产前患病率为0.039%-0.087%。大多数孤立的轻度脑室增宽（MV）胎儿（>90％）具有良好的预后。然而,患有孤立性MV的胎儿中有5.6％至7.9％的胎儿具有不良的神经发育结局。在这项研究中,我们报道了第一例产前SnijdersBlok-Fisher综合征(OMIM:#618604),该综合征是由POU3F3的截断变异体(OMIM:*602480)在胎儿中引起的,其具有短暂的双侧孤立MV。核型分析结果,染色体微阵列分析,胎儿TORCH感染评价均为阴性。然而,NM_006236.3(POU3F3):c.640C>T[rs1254251078]p.(Q214*)的从头可能致病性无义变体通过全外显子组测序(WES)鉴定。尽管有足够的遗传咨询，母亲拒绝进行进一步的脑磁共振成像（MRI），并决定保留胎儿。她通过足月阴道分娩生下了一名男婴。通过长期随访，不幸的是，婴儿逐渐出现运动发育迟缓。先证者的出生后脑MRI显示call体发育不良和脑室肿大。考虑到此类病例误诊的可能性很高，我们进一步总结了19例报道的POU3F3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,而仅约26.32％的胎儿表现出MV或囊肿，而没有结构畸形。因此，我们的发现扩展了POU3F3的变异谱，并表明当胎儿分离出双侧MV时，进行WES和脑MRI的重要性。
