A study led by investigators from Shinshu University in Nagano, Japan, has made a key discovery about the mechanism that causes microcephaly with pontine and cerebellar hypoplasia (MICPCH), a rare genetic disorder affecting brain development.
One of 2 CASK-related intellectual disabilities, MICPCH is a rare condition, with only 53 cases in females and 7 cases in males to date described in literature. Symptoms of the disorder include an unusually small head at birth that does not grow at the same rate as the body, severe intellectual disability, underdevelopment in the brain’s cerebellum and pons, seizures, sleep disturbances, vision and hearing loss, and decreased muscle tone. MICPCH is caused by mutations in the gene providing instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK), and the CASK gene is located on the X chromosome. The protein is mostly found in neurons and helps control the expression of genes that are important to brain development.
“In our study, we found an increase in the excitatory synaptic function and decrease in the inhibitory synaptic function only in CASK mutant neurons, but not in wild-type neurons in the same brain,” added Tabuchi.
The study team found that the imbalance is caused by a decrease in concentration of a specific receptor on the membrane that receives signals from other neurons, and increasing the concentration restored balance. The findings, said Tabuchi, may have important implications for other mental disorders such as autism or epilepsy.