Morphometric variability of neuroimaging features in Children with Agenesis of the Corpus Callosum

To address the variability of corpus callosum abnormalities we present a neuroimaging series of 201 individuals with ACC. Our data mirrors previously published data indicating that nearly one-in-five individuals diagnosed with ACC at a tertiary care hospital have complete agenesis or CAG [3]. These individuals were younger than those with hypoplasia or dysplasia possibly because CAG is more easily identified on prenatal ultrasound screening than in the hypoplasia or dysplasia group [12, 13]. However, there is selection bias inherent because our study did not include prenatal cases of ACC, of which up to 42.4 % are terminated prior to birth [14].

Colpocephaly was more frequent in CAG than in the hypoplasia or dysplasia group. It is caused by decreased white matter in the occipital cortex leading to secondary expansion of the posterior horns of the lateral ventricles [8, 15]. The preservation of myelinated callosal tracts in the hypoplasia or dysplasia group likely provides structural integrity preventing posterior expansion of the lateral ventricles. Probst bundles were more frequent in CAG than in the hypoplasia or dysplasia group. Probst bundles are longitudinal axonal fiber tracts of the corpus callosum that have failed to cross the midline into the contralateral hemisphere and form ectopic fiber bundles along the dorsomedial lateral ventricular surface [15, 16]. Increased thickness of Probst bundles, given the absence of crossing fibers in CAG, is likely to account for its visualization on MRI. Hippocampal anomalies were more frequent in CAG versus in the hypoplasia or dysplasia group. Developmental studies in mice demonstrate that incipient axonal collaterals from the hippocampal primordium serve as “guideposts” for subsequent callosal axons to cross into the contralateral hemisphere [16, 17]. Therefore, disruptions in hippocampal development may indirectly cause early and severe disruptions in callosal development leading to CAG. White matter anomalies were also more frequent in the hypoplasia or dysplasia group versus CAG. Initial callosal tracts are established prior to the beginning of myelination thereby mechanisms guiding myelination would not be expected to contribute to widespread corpus callosum abnormalities [15]. However, CAG has been reported with cholesterol biosynthesis aberrations suggesting that white matter abnormalities can lead to CAG as well [18].

The use of the refined classification system by Hanna et al [9] provides many advances in the investigation of the causes of ACC. The heterogeneity of callosal morphologies is more accurately described by the inclusion of subclasses of corpus callosum abnormalities and almost sufficient to characterize our entire cohort. One exception was the rudimentary body abnormality, which lacks rostral callosal components. As rostral and caudal regions of the corpus callosum are thought to be regulated by separate developmental mechanisms, this subclass likely has a unique genetic mechanism [16].