Distinguishing 3 classes of corpus callosal abnormalities in consanguineous families

The corpus callosum (CC) structurally consists of 4 major anatomic features including the rostrum, genu, corpus, and splenium (figure 1). Corpus callosal abnormalities (CCA), a term encompassing agenesis of the corpus callosum (ACC), has an estimated prevalence of 0.3%–0.7% in patients undergoing brain imaging,1 but in Middle Eastern populations the prevalence is probably closer to 1%,2,3 due to the higher rates of inbreeding. The finding of CCA can be identified incidentally, or can be part of a developmental or cytogenetic disease. Figure 1 Classification of morphologic spectrum of midline sagittal MRI appearance of the corpus callosum (CC) Previous studies have differentiated CCA into those with or without additional brain malformations3 or into partial or complete agenesis.4 However, in one study, roughly equal percentages of patients with either partial or complete agenesis displayed additional structural brain abnormalities, suggesting that this differentiation may not relate to causative etiology.5 The presence vs absence of Probst bundles (PBs) has also been used to define categories of disease,3 but has not been validated as a clinically predictive sign. CCA was previously divided into hypogenesis (incomplete formation) and dysgenesis (defective development),6 but further segregation based upon these initial findings has not been explored. We aimed to refine this classification system, to account for similarities in CC appearance in affected siblings within a single family, where a common genetic etiology is most likely. Since recessive forms of disease (i.e., those observed in families with documented consanguinity and a recessive mode of inheritance) are the most likely to show consistent CC appearance, and are most often due to loss-of-function alleles (rather than environmental or dominant causes), the minimized intrafamilial variability could help determine the relationship between primary gene mutation and CCA morphology.