Genetic mutation: Brugada syndrome type 1 is sometimes caused by mutations or defects in the SCN5A gene. The SCN5A gene provides instructions for making a cardiac sodium channel, a protein essential to the normal electrical functioning and rhythm of the heart. The sodium channel normally transports positively charged sodium 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. Only about one-third of people with Brugada syndrome have been identified as having a mutated copy of this gene.
Brugada syndrome type 2 is caused by a mutation in the GPD1L gene. This mutation decreases the expression of the sodium channel on the cell surface, resulting in reduced inward sodium current and abnormal heart function.
Brugada syndrome type 3 is caused by a mutation in the CACNA1C gene. This gene belongs to a family of genes that provide instructions for making calcium channels. These channels, which transport positively charged calcium ions into cells, play a key role in the cell's ability to generate and transmit electrical signals.
Brugada syndrome type 4 is caused by a mutation in the CACNB2 gene, a subunit of the L-type cardiac calcium channel. A mutation in this gene can lead to a shorter-than-normal QT interval, resulting in a faster heart rate.
Random occurrence: In some cases, Brugada syndrome occurs in an individual with no family history of the disease. This is caused by a spontaneous genetic mutation in the sperm or egg cells or in the developing embryo. People who acquire Brugada syndrome as the result of a spontaneous mutation may be able to pass on the syndrome to their children.
Other: In rare cases, Brugada syndrome has been caused by abnormally low potassium levels or abnormally high calcium levels in the blood.
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