The discovery was made when researchers examined a pair of siblings who had developed normally from a physical standpoint but suffered from neurodevelopmental delay and sudden, unexplained seizures and convulsions. The problem was so bad that neither had learned how to walk or speak.
The researchers theorized that the source of these symptoms was genetic. Eventually they found that both siblings showed a recessive mutation in the CAMK2A genes – which have been linked to regulation of learning and memory in animals.
Senior author Bruno Reversade says that these types of discoveries aren’t uncommon; in fact, he says that they can often lead to the development of better treatments.
“A significant number of children are born with growth delays, neurological defects and intellectual disabilities every year across the world,” he said. “While specific genetic mutations have been identified for some patients, the cause remains unknown in many cases. Identifying novel mutations would not only advance our understanding of neurological disease in general but would also help clinicians diagnose children with similar symptoms and/or carry out genetic testing for expecting parents.”
Treating undiagnosed patients
For this disorder, the researchers say that a single coding error in the CAMK2A gene prevented protein subunits from assembling correctly. Further study with roundworms confirmed that this mutation can disrupt neuronal communication and the development of normal motor function.
Co-first author Franklin Zhong hopes that his team can bring these findings to experts in pediatric genetics so that undiagnosed children with similar symptoms can be identified and helped more effectively.
“Neuroscientists working to understand childhood brain development, neuronal function, and memory formation also need to consider this new disease, since CAMK2A is associated with these processes,” he said.
“In the future, it would be interesting to test whether restoring CAMK2A activity can bring therapeutic benefit to patients with this condition, as well as those with related neurological disorders.”
The full study has been published in the journal eLife.