Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes

The corpus callosum is the largest fibre tract in the brain, connecting the two cerebral hemispheres, and thereby facilitating the integration of motor and sensory information from the two sides of the body as well as influencing higher cognition associated with executive function, social interaction and language. Agenesis of the corpus callosum is a common brain malformation that can occur either in isolation or in association with congenital syndromes. Understanding the causes of this condition will help improve our knowledge of the critical brain developmental mechanisms required for wiring the brain and provide potential avenues for therapies for callosal agenesis or related neurodevelopmental disorders. Improved genetic studies combined with mouse models and neuroimaging have rapidly expanded the diverse collection of copy number variations and single gene mutations associated with callosal agenesis. At the same time, advances in our understanding of the developmental mechanisms involved in corpus callosum formation have provided insights into the possible causes of these disorders. This review provides the first comprehensive classification of the clinical and genetic features of syndromes associated with callosal agenesis, and provides a genetic and developmental framework for the interpretation of future research that will guide the next advances in the field.