Cerebral Ventriculomegaly With Abnormality of the Aqueduct of Sylvius: A Case Series

ABSTRACT Fetal cerebral ventriculomegalies are brain anomalies with potentially poor neurodevelopmental prognosis. They are amenable to prenatal imaging, isolated or associated with other cerebral and/or extra‐cerebral abnormalities. Most are obstructive due to a focal or diffuse dysgenesis of the ventricular system, disturbing the cerebro‐spinal fluid outflow. Triventricular dilatation is the most common, predicting a lesion at the level of the aqueduct of Sylvius (AS). Although variants in several genes have recently been linked to ventriculomegaly, their role remains unclear, compromising our ability to predict the impact of such variations when detected prenatally. To go further, we report here a monocentric cohort of 51 fetuses with cerebral ventriculomegaly linked to dysgenetic AS and discuss phenotype/genotype correlations after neuropathological study. A genetic cause has been identified in 15 cases (29.4%) using different genetic methods available between 1992 and 2021: standard karyotyping, targeted mutation screening (Sanger sequencing), and Next Generation Sequencing. Dysgeneses of the AS are still controversial in their nosology and etiology; most are discussed on the basis of brain imaging findings alone. In this series, complete fetal and neuropathological examination allowed detection of key clinical and histopathological clues, allowing the orientation of molecular screenings and the identification of cellular mechanisms involved in triventricular dilatations.