Complete agenesis of corpus callosum and unilateral cortical formation anomalies detected on fetal MR imaging: a phenotype strongly associated with the male fetuses

Introduction: In a previous study of classifying fetuses with cortical formation abnormalities (CFA) with fetal MR, we noticed a cluster of cases with unilateral CFA and complete agenesis of the corpus callosum (ACC). In this study, we provide a detailed morphological analysis of such fetuses using fetal MR to determine if there are indicators (such as the gender of the fetus) that could be used to delineate a genetic substrate of the phenotype in order to inform future studies. Methods: We have studied 45 fetuses with the unilateral CFA/ACC phenotype and analysed through an expert consensus panel the location and fine detail of the CFA and the associated findings such as associated anomalies, head size, and sex of the fetus. Results: The frontal lobe was significantly more frequently involved by CFA when compared with other lobes (p < 0.001) but no preference for the left or right hemisphere. CFA most often consisted of excessive/dysmorphic sulcation. The CFA/ACC phenotype was overwhelmingly more frequent in male fetuses (M:F 4.5:1—p < 0.0001). The most frequent associated findings were: ventriculomegaly (16/45 fetuses) and interhemispheric cysts (12/45 cases). Conclusions: This report highlights the specific phenotype of unilateral CFA/ACC that is much more common in male fetuses. This finding provides a starting point to study possible sex-linked genetic abnormalities that underpin the unilateral CFA/ACC phenotype. Key Points: • We collected fetuses with unilateral cortical formation abnormality and callosal agenesis. • That distinctive neuroimaging phenotype has a strong male gender prevalence (over 80%). • This observation forms the basis of studies about outcomes and genetic substrates.