What are the genetic changes related to Brugada syndrome ?
Brugada syndrome can be caused by mutations in one of several genes. The most commonly mutated gene in this condition is SCN5A, which is altered in approximately 30 percent of affected individuals. This gene provides instructions for making a sodium channel, which normally transports positively charged sodium atoms (ions) into heart muscle cells. This type of ion channel plays a critical role in maintaining the heart's normal rhythm. Mutations in the SCN5A gene alter the structure or function of the channel, which reduces the flow of sodium ions into cells. A disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of Brugada syndrome.  Mutations in other genes can also cause Brugada syndrome. Together, these other genetic changes account for less than two percent of cases of the condition. Some of the additional genes involved in Brugada syndrome provide instructions for making proteins that ensure the correct location or function of sodium channels in heart muscle cells. Proteins produced by other genes involved in the condition form or help regulate ion channels that transport calcium or potassium into or out of heart muscle cells. As with sodium channels, proper flow of ions through calcium and potassium channels in the heart muscle helps maintain a regular heartbeat. Mutations in these genes disrupt the flow of ions, impairing the heart's normal rhythm.  In affected people without an identified gene mutation, the cause of Brugada syndrome is often unknown. In some cases, certain drugs may cause a nongenetic (acquired) form of the disorder. Drugs that can induce an altered heart rhythm include medications used to treat some forms of arrhythmia, a condition called angina (which causes chest pain), high blood pressure, depression, and other mental illnesses. Abnormally high blood levels of calcium (hypercalcemia) or potassium (hyperkalemia), as well as unusually low potassium levels (hypokalemia), also have been associated with acquired Brugada syndrome. In addition to causing a nongenetic form of this disorder, these factors may trigger symptoms in people with an underlying mutation in SCN5A or another gene.