What do we know so far about disorders of the corpus callosum?

We know that the process of wiring up the brain begins prior to birth, with the first axons beginning to form the corpus callosum as early as 10-12 weeks of gestation. The corpus callosum grows in size both during gestation and after birth, continuing to connect neurons in each hemisphere, until a fully functioning brain is formed. Malformations of the corpus callosum usually arise during embryonic and foetal development.

Everything we know about the corpus callosum and its development has come from scientific research. We have identified a number of developmental processes required to form the corpus callosum, and that must occur in the correct sequence. We know that similar processes occur in the brains of animals, such as mice, as they form their corpus callosum. We know that genes and molecules regulate the different developmental steps. Scientists have identified over 60 genes that are important for the formation of the corpus callosum in mice, but we have not yet been able to translate this knowledge into understanding how the corpus callosum forms in human beings. Only a handful of genes have been discovered that regulate corpus callosum formation in humans. More research with human subjects is needed to bridge the gap between what we are learning by studying mouse models and what we know about the formation of the corpus callosum in human beings. To facilitate this we need more information about this condition in people and recent advances in neuro-imaging (MRI) and genetics has made this work possible.

What do we know about the implications of dysgenesis of the corpus callosum?

Surprisingly, even though the corpus callosum is the largest fibre tract in the brain, it is not required for survival. This is because it does not transmit information about essential life processes such as breathing and heart rate. It is instead involved in processing information that is primarily processed in the cerebral cortex, an area of the brain that is mostly involved in higher cognitive functions. A complete lack of formation of the Corpus Callosum or a malformation can have a wide range of behavioural and neuropsychological implications: deficits in social interaction, problems with language development, sleep, reading and writing, and memory. More severe cases can have deficits in sensory and motor processes, where children don’t learn to walk, or have visual or hearing impairments. Some people have very few deficits and may not even realize that they were born without a corpus callosum. In these cases it is possible that during brain development, the axons of the corpus callosum found an alternative way to cross the midline, a process included in the concept of brain ‘plasticity’. Much research is being directed at the moment to understand this process, and we now have newer technologies that will allow us to study this in human brains.

Will we ever cure defects in corpus callosum development?

This is difficult to answer since we have so little knowledge about the mechanisms involved in the normal formation of the corpus callosum. As in any other area of medical research, understanding the developmental processes and identifying the genes and molecules that regulate these events, will enable us to identify possible therapies. Ongoing research in mice is trying to determine if the corpus callosum can be repaired by replacing the affected genes. Another area of research is to develop genetic tests that can be used to identify what gene might be disrupted in patients with corpus callosum defects. Early diagnosis of these gene deficiencies may help doctors and their patients and families to provide a more accurate prognosis and to develop early intervention strategies to help with expected cognitive deficits. Through scientific research we can answer these questions but it takes time and money to conduct the experiments. The incidence of corpus callosum agenesis is 1:4000 in the USA and it is expected that the same incidence would be found in Australia. Thus, this is a relatively rare disorder and so most studies conducted so far have involved smaller groups of people.

How can individuals with dysgenesis of the corpus callosum help our research?

At present we initially aim to collect information from people who have been diagnosed with agenesis or dysgenesis of the corpus callosum. Our aim is to survey the Australian population of ACC patients to assess the range of disorders associated with callosal malformations in Australia. If you are willing to participate in this study we would love to hear from you. You can download an information sheet on the project with further instructions on how to participate here, and you will be asked to fill in a questionnaire and consent form, click here to download as pdf file, or here to download a Word file.

Contact Prof. Richards for further details.