SCN5A

The SCN5A gene belongs to a family of genes that provide instructions for making sodium channels. These channels, which transport positively charged sodium atoms (sodium ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals..

The SCN5A gene provides instructions for making a sodium channel that is abundant in heart (cardiac) muscle. These channels open and close at specific times to control the flow of sodium ions into cardiac muscle cells. By changing the electrical properties of these cells, sodium channels play a major role in signaling the start of each heartbeat, coordinating the contractions of the upper and lower chambers of the heart, and maintaining a normal heart rhythm.

Brugada syndrome - caused by mutations in the SCN5A gene

More than 80 mutations in the SCN5A gene have been identified in people with Brugada syndrome and a condition called sudden unexpected nocturnal death syndrome (SUNDS). SUNDS was originally described in Southeast Asian populations, but researchers have since determined that SUNDS and Brugada syndrome are the same disorder.

Some SCN5A mutations change single protein building blocks (amino acids) in the SCN5A protein. These mutations alter the structure of ion channels made with the SCN5A protein and disrupt the flow of sodium ions into cardiac muscle cells. Other mutations prevent the SCN5A gene from producing any functional ion channels, which also reduces the inward flow of sodium ions. A disruption in ion transport changes the way the heart beats, leading to the abnormal heart rhythm (arrhythmia) often found in Brugada syndrome and SUNDS.

Romano-Ward syndrome - caused by mutations in the SCN5A gene

At least 30 mutations in the SCN5A gene are known to cause a form of Romano-Ward syndrome called long QT syndrome type 3 (LQT3). These mutations include changes in single amino acids and deletions or insertions of a small number of amino acids in the SCN5A protein. Channels made with these altered SCN5A proteins stay open longer than usual, which allows sodium ions to continue flowing into cardiac muscle cells abnormally. This delay in channel closure disrupts the heart's normal rhythm, leading to the irregular heartbeat characteristic of Romano-Ward syndrome.

other disorders - caused by mutations in the SCN5A gene

Mutations in the SCN5A gene are responsible for several other heart rhythm abnormalities. These conditions include cardiac conduction disease, sick sinus syndrome, sudden infant death syndrome (SIDS), and acquired long QT syndrome.

Cardiac conduction disease is a heart condition that increases the risk of fainting (syncope) and sudden death. This condition is caused by SCN5A mutations that lead to a partial or total loss of sodium channel function, reducing or stopping the flow of sodium ions into cardiac muscle cells. Cardiac conduction disease is inherited in an autosomal dominant pattern, which means one altered copy of the SCN5A gene in each cell is sufficient to cause the disorder.

Sick sinus syndrome is a disorder of the sinoatrial node, which is a group of specialized cells in the heart that function as a natural pacemaker. The sinoatrial node cannot effectively regulate the heartbeat in people with this condition, leading to an abnormally slow heart rhythm (bradycardia) and an increased risk of dizziness and fainting. Mutations in the SCN5A gene that cause sick sinus syndrome produce nonfunctional sodium channels or abnormal channels that cannot transport ions properly. Sick sinus syndrome is inherited in an autosomal recessive pattern, which means two copies of the gene must be altered in each cell for a person to be affected by the condition.

SIDS is a major cause of death in babies younger than one year. It is characterized by sudden and unexplained death, usually during sleep. Although the cause of SIDS is often unknown, researchers have identified mutations in the SCN5A gene in some cases of this condition. Other genetic and environmental factors, many of which have not been identified, also play a part in determining the risk of SIDS.

Certain drugs, including medications used to treat arrhythmias, infections, seizures, and psychotic disorders, can lead to an abnormal heart rhythm in some people. This drug-induced heart condition, which is known as acquired long QT syndrome, increases the risk of cardiac arrest and sudden death. A small percentage of cases of acquired long QT syndrome occur in people who have an underlying mutation in the SCN5A gene.