In a study published in Nature Genetics, Dr Saumya Jamuar, co-founder of Global Gene Corp and a visiting scientist at Harvard Medical School, under the supervision of Prof Christopher Walsh and A/Prof Timothy Yu of Harvard Medical School, reports on a new disease entity that they discovered in their quest to map novel human disorders related to brain development.
The new syndrome, referred to as ‘Developmental Split-Brain syndrome’ is caused by biallelic mutations in the human Deleted in Colorectal Carcinoma (DCC) gene. It can lead to symptoms including intellectual disability, horizontal gaze palsy, mirror movements and scoliosis. This disorder affects individuals soon after birth (and in case 3, even during pregnancy) although the clinical features may not be obvious until an older age.
The hallmark feature of this syndrome is the distinct pattern on brain imaging, and includes agenesis of corpus callosum, absent anterior and hippocampal commissures and ventral midline brain malformations.
Although, this condition is rare, the phenomenon of split brain has been intensely studied with implications on brain organization. There are also explicit connections between split brains and neurodevelopmental disorders, including autism and Asperger syndrome. The findings may also have implications in improving our understanding of common disorders such as scoliosis and strabismus.
The discovery is as a result of an international collaborative effort to study the DCC gene in three families from different regions of the globe (Mexico, USA and Saudi Arabia) who remarkably shared similar clinical and radiological features. On detailed neuroimaging, the team discovered that the central defect was lack of connection between the right and left side of the brain (technical term: disruption of midline commissural tracts).
“This work highlights the need for international collaborative work by building networks and integrating deep clinical and radiological information into research.” says Dr Jamuar. “After working on family 1, we reached out to our collaborators and were struck by the similarity between the images of family 1 and family 2. That’s when we realized that we had found a novel disease entity. The imaging, plus other findings in our patients, demonstrates that the left and right halves of the brain lack the structures necessary to talk to one another — effectively splitting it into two separate halves.”
“It was really exciting when we saw the mutation in DCC— a reunion with an old scientific friend,” says Yu, who studied the gene in roundworms as a graduate student in the 1990s. “At a symposium nearly 20 years ago, I had to explain to an audience full of parents and pediatricians how this really elementary work might relate to their children and patients with autism and ADHD. I talked about how one day we may find that the fundamental mechanisms controlling the wiring of neural circuitry could be disrupted in human neurodevelopmental disorders, too — but it was all theoretical. Finding the complete knockout now feels like it completes the circle.”
The researchers will continue to search for more such patients who may have aberrations along the same genetic pathway, and hope that their findings will help improve the understanding of how the brain develops.