Cabet Sara, Ghersi-Egea Jean-François, Khung-Savatovsky Suonavy, Guimiot Fabien, Putoux Audrey, Sabatier Isabelle, Fernandez Carla, Raymond Laure, Mortreux Jérémie, Laurichesse Delmas Hélène, Cuillier Fabrice Eric, Ho Fabien, Lesca Gaetan, Alessandri Jean-Luc, Guibaud Laurent
Pediatric and Fetal Imaging Department, Femme-Mère-Enfant Hospital, Hospices Civils de Lyon, Claude Bernard Lyon 1 University, 69500 Lyon, France.
Institut NeuroMyoGène, CNRS UMR5292, INSERM U1028, Claude Bernard Lyon 1 University, 69500 Lyon, France.
Genes (Basel). 2025 Jun 13;16(6):707. doi: 10.3390/genes16060707.
Ventriculomegaly is the main prenatal imaging feature for diagnosing fetal central nervous system anomalies in humans. Many ventriculomegalies can be related to genetic causes, regardless of their imaging presentations. Among these, variants have been reported to cause severe ventriculomegaly inherited in an autosomal recessive manner (OMIM#615219). Several hypotheses have been put forward linking variants to ventriculomegaly, but the precise underlying mechanisms, in particular whether its origin is obstructive or non-obstructive, are yet to be elucidated.
To address this question, we retrospectively analyzed pre- and postnatal neuro-imaging and neuropathological data for cases of ventriculomegaly in which variants were found through exome or genome sequencing. We performed anti-MPDZ immunostaining on fetal brain samples.
We analyzed six cases (four fetuses and two children) of ventriculomegaly of variable severities with variants. The precise analysis of brain MRI data, corroborated by fetopathological examinations, demonstrated an obstructive pattern of ventriculomegaly upstream from partial fusion of the thalami, also called diencephalosynapsis, with partial atresia of the third ventricle, which could extend to Sylvius's aqueduct.
The morphological analysis using targeted brain magnetic resonance imaging (MRI) and neuropathological data allowed us to unravel the underlying mechanisms of congenital ventriculomegaly related to variants.
脑室扩大是诊断人类胎儿中枢神经系统异常的主要产前影像学特征。许多脑室扩大可能与遗传因素有关，无论其影像学表现如何。其中，已报道某些变异以常染色体隐性方式遗传导致严重脑室扩大（OMIM#615219）。已经提出了几种将这些变异与脑室扩大联系起来的假说，但确切的潜在机制，特别是其起源是梗阻性还是非梗阻性，尚待阐明。
为了解决这个问题，我们回顾性分析了通过外显子组或基因组测序发现存在这些变异的脑室扩大病例的产前和产后神经影像学及神经病理学数据。我们对胎儿脑样本进行了抗MPDZ免疫染色。
我们分析了6例存在这些变异的不同严重程度的脑室扩大病例（4例胎儿和2例儿童）。脑MRI数据的精确分析得到胎儿病理学检查的证实，显示在丘脑部分融合（也称为间脑融合）上游存在梗阻性脑室扩大模式，伴有第三脑室部分闭锁，可延伸至中脑导水管。
使用靶向脑磁共振成像（MRI）和神经病理学数据进行的形态学分析使我们能够揭示与这些变异相关的先天性脑室扩大的潜在机制。
