Brugada syndrome ... (Brugada Syndrome) - Genes SCN5A, GPD1L, CACNA1C, CACNA2D1, CACNB2, HCN4, KCND3, KCNE3, KCNE5, KCNJ8, RANGRF, SCN1B, SCN2B, SCN3B, SLMAP and TRPM4.  

Brugada syndrome is a disease characterized by an abnormal heart rhythm, due to uncoordinated electrical activity in the ventricles (ventricular arrhythmia). This alteration affects both sexes equally, although it seems to have a higher incidence in males, a difference that seems to be attributed to the high levels of testosterone. If altering the rhythm of the heartbeat left untreated can cause syncope, seizures, difficulty breathing, or sudden death. These complications occur when the person is at rest or asleep.

Overall, this syndrome is evident in adulthood, although their signs and symptoms, including sudden death, can occur anytime from childhood to old age. The mean age of sudden death syndrome usually occurs at age 40. This process may explain some cases of sudden death in infancy (SIDS: Sudden Infant Death Syndrome), which is the leading cause of death in children under one year. It is characterized by a sudden and unexpected death, usually during sleep. Unexplained nocturnal sudden death (SUNDS: Sudden Unexplained Nocturnal Death Syndrome) is characterized by an unexpected cardiac arrest in young adults, usually at night while sleeping. Initially, this syndrome was described in inhabitants of Southeast Asia, where it is the leading cause of death. It has been shown that SUNDS Brugada syndrome correspond to the same alteration.

This syndrome may be due to mutations in one of several genes. The mutated gene responsible for most cases (30%) is the SCN5A gene, located on the short arm of chromosome 3 (3p21). This gene belongs to the family of genes SCN (Sodium cannel, voltage-gated, type V, alpha subunit) that encode proteins intended to form sodium channels. These channels convey sodium positively charged ions into cardiac muscle cells and have a primary role in the ability of cells to generate and transmit electrical signals, regulating heart 's normal rhythm. Sodium channel of cardiac muscle open and close to control the flow of ions into cardiac muscle cells. By changing the electrical properties of these cells, the sodium channels have a central role for the initiation of the heartbeat, coordinating atrial and ventricular contractions, and maintaining normal heart rhythm.

They have identified more than 300 mutations in the SCN5A gene in people with Brugada syndrome and people affected by SUNDS. Mutations in this gene alter the structure or function of these channels, which reduces the flow of ions into cells, and consequently the frequency of the heartbeat, causing an abnormal rhythm characteristic of the syndrome.

Mutations in other genes may also cause Brugada syndrome: GPD1L, CACNA1C, CACNA2D1, CACNB2, HCN4, KCND3, KCNE3, KCNE5, KCNJ8, RANGRF, SCN1B, SCN2B, SCN3B, SLMAP and TRPM4. Together, these other genetic changes less than 2% of cases of the disease. Some of the genes involved in additional Brugada syndrome encode proteins that ensure the correct location or function of sodium channels in heart muscle cells. The proteins encoded by other genes involved in the shape or condition help regulate ion channels that transport calcium or potassium inside or outside of the heart muscle cells. As with the sodium channels, the appropriate ion flux through calcium channels and potassium in the heart muscle helps maintain a regular heartbeat. Mutations in these genes disrupt the flow of ions, by affecting the normal heart rhythm.

In those affected without an identified genetic mutation it is unknown often the cause of Brugada syndrome. In some cases, certain drugs can cause acquired form nongenetic, the syndrome, as with drugs used to treat arrhythmias, cardiac angina, high blood pressure, depression and other mental illnesses. They have also been associated with Brugada syndrome, elevated blood calcium (hypercalcemia), or potassium (hyperkalaemia) and very low concentrations of potassium (hypokalemia). These circumstances may also precipitate symptoms, when there is an underlying mutation SCN5A gene or another gene.

This process is inherited as an autosomal dominant, ie the existence of a single altered copy of the gene in each cell is sufficient to express the disease. In most cases, an affected, has an affected parent. In other cases, there may be new mutations in the gene, when there are no known cases in the family.

Tests performed in IVAMI: in IVAMI perform the detection of mutations associated with Brugada syndrome, by complete PCR amplification of the exons of SCN5A, GPD1L, CACNA1C, CACNA2D1, CACNB2, HCN4, KCND3, KCNE3, KCNE5, KCNJ8 genes , RANGRF, SCN1B, SCN2B, SCN3B, SLMAP and TRPM4, respectively, and subsequent sequencing. We recommend starting the study by exons of SCN5A gene, responsible for 30% of cases of the disease. If not, it is suggested further by sequencing the remaining genes to optimize the best time / cost.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).