The corpus callosum is the largest fibre tract in the human brain and connects neurons in the left and right hemispheres of the brain. Its function is to integrate information from both sides of the brain, making the brain more efficient at processing sensory and motor information, and in performing complex tasks such as communication (verbal and non-verbal) and social and emotional intelligence.

Developmental disorders of the corpus callosum can be found in isolation, where only the corpus callosum is affected, or together with other brain abnormalities as part of a syndrome. To date, over 300 different syndromes possibly involving a corpus callosum anomaly have been described, but the genetic bases of 70 have been identified, while no single gene responsible for isolated DCC is known. While each syndrome has an additional unique set of brain and/or body features, systematic study of their shared genetic and neurodevelopment features should provide insight regarding the mechanisms that cause disrupted callosal development. Developmental disruption of the corpus callosum, known as dysgenesis or disorders of the corpus callosum (DCC), can occur prior to, or shortly following birth.

Based on data from the state of California, and our cohort information, the estimated incidence of DCC is approximately 1 in every 3000 live births. The cause of these disorders is likely largely genetic, with cases of both inherited (recessive) genetic mutations and dominant de novo mutations (meaning mutations that occur in only the affected person and are not inherited) being identified.

Today, DCC can be identified as early as 20 weeks of gestation by ultrasound or magnetic resonance imaging (MRI). Sadly, the identification of callosal dysgenesis at this stage of life is of limited value to families or the clinician treating them, because callosal dysgenesis alone cannot predict the long-term cognitive or behavioral impact to the child. To maximize the benefit of early diagnosis, there is a pressing and urgent need to discover the genetic cause of these disorders

Callosal dysgenesis affects the individual throughout life, as it is a structural change in the way the brain is wired from the earliest stages of brain development. Most individuals diagnosed with callosal disorders after birth are either moderately or severely affected. A small proportion never learn to walk or talk, and many can achieve these goals but are delayed in meeting those developmental milestones.  Most people affected will have ongoing delays in learning, below expected intelligence and behavioral problems, often similar to those seen in autism spectrum disorder. DCC is very commonly associated with social difficulties that become evident in adolescence and adulthood, and can lead to social isolation and difficulty maintaining friendships and employment. Even individuals with DCC who have average or higher than average intelligence are at risk of having difficulties in social competence, which in turn significantly limit their capacity to function independently in adulthood. As we gain a better understanding of how DCC impacts cognitive and behavioral development, we can provide families with more accurate predictions about the challenges a child with DCC may face, as well as better tools for overcoming those challenges.

It is striking that some individuals with DCC are able to partially compensate despite disruption of this major brain fibre tract. We expect answers to that puzzle can be found in detailed mapping of how the brains of these individuals have rewired to cope with these challenges. Using sophisticated ways of studying brain wiring with MRI, it is now possible to identify changes in callosal connectivity (that is how different areas of the brain are linked together to produce complex functions like communication and social competence) and how these may be linked to an overall disruption in cerebral connectivity. It is therefore of keen scientific interest to understand how the brain wiring is changed, perhaps in either a compensatory or in a deleterious way, and how these changes impact the cognitive function of the individual. Understanding the mechanisms behind these alterations in brain development could help scientific investigators discover the fundamental basis of brain development and wiring, and the genetic mechanisms that control these events, as well as how both of these underlie brain function. This line of study could be a critical first step on the road toward finding treatments for these disorders in patients with callosal dysgenesis and disorders with related alterations in brain wiring, such as autism and schizophrenia.