What are the genetic changes related to juvenile myoclonic epilepsy ?
The genetics of juvenile myoclonic epilepsy are complex and not completely understood. Mutations in one of several genes can cause or increase susceptibility to this condition. The most studied of these genes are the GABRA1 gene and the EFHC1 gene, although mutations in at least three other genes have been identified in people with this condition. Many people with juvenile myoclonic epilepsy do not have mutations in any of these genes. Changes in other, unidentified genes are likely involved in this condition.  A mutation in the GABRA1 gene has been identified in several members of a large family with juvenile myoclonic epilepsy. The GABRA1 gene provides instructions for making one piece, the alpha-1 (1) subunit, of the GABAA receptor protein. The GABAA receptor acts as a channel that allows negatively charged chlorine atoms (chloride ions) to cross the cell membrane. After infancy, the influx of chloride ions creates an environment in the cell that inhibits signaling between nerve cells (neurons) and prevents the brain from being overloaded with too many signals. Mutations in the GABRA1 gene lead to an altered 1 subunit and a decrease in the number of GABAA receptors available. As a result, the signaling between neurons is not controlled, which can lead to overstimulation of neurons. Researchers believe that the overstimulation of certain neurons in the brain triggers the abnormal brain activity associated with seizures.  Mutations in the EFHC1 gene have been associated with juvenile myoclonic epilepsy in a small number of people. The EFHC1 gene provides instructions for making a protein that also plays a role in neuron activity, although its function is not completely understood. The EFHC1 protein is attached to another protein that acts as a calcium channel. This protein allows positively charged calcium ions to cross the cell membrane. The movement of these ions is critical for normal signaling between neurons. The EFHC1 protein is thought to help regulate the balance of calcium ions inside the cell, although the mechanism is unclear. In addition, studies show that the EFHC1 protein may be involved in the self-destruction of cells. EFHC1 gene mutations reduce the function of the EFHC1 protein. Researchers suggest that this reduction causes an increase in the number of neurons and disrupts the calcium balance. Together, these effects may lead to overstimulation of neurons and trigger seizures.