Childhood epilepsy affects roughly 4% of the pediatric population, and there are many different types of epilepsy and seizure frequency and intensity. 20% of patients have intractable epilepsy, which means that pharmaceutical treatments have failed to control seizure activity. A recent study published in Nature Genetics attributes the cause of mysterious seizure conditions to malformations of cortical development (MCD). Scientists believe that seizure activity may originate in these patches of damaged or abnormal brain tissue. MCD resection can reduce or prevent seizures for patients with intractable epilepsy, but researchers believe a closer examination of the mechanisms involved in seizure activity will lead to future effective therapies.
Researchers at the University of California San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine collaborated to explore the genetic causes of MCD. They collaborated with an international consortium of more than 20 children’s hospitals worldwide. Members of the Focal Cortical Dysplasia Neurogenetics Consortium examined 283 brain resections from children across a range of MCD types to identify potential genetic causes. The consortium organized a biobank to store tissue for high-throughput analysis, and the researchers looked for mutations present in a small subset of brain cells called genetic somatic mosaicism. Previous research indicated that genetic somatic mosaicism in the mTOR signaling pathway was a contributing factor. The team identified 69 different genes carrying somatic brain mutations. Genes converged on calcium signaling, gene expression, and synaptic functions.
First study author Dr. Changuk Chung explains the relevance of cancer research to approaches to researching epilepsy. According to Chung, “We can draw parallels with the cancer field because these mutations disrupt cellular function and need to be respected. However, unlike cancer cells, brain cells mostly do not divide, so these cells misbehave by stimulating epileptic seizures. The question that arose was whether the newly found gene mutations were sufficient to cause MCD disease.” When the mutations were introduced into a mouse model, abnormalities similar to those seen in patients were observed. The findings could be used to improve diagnosis and develop cures for MCD disease.
Sources:
Eureka News Alert, Nature Genetics