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Long QT Syndrome Symptoms Causes Treatment

Inherited Long QT Syndrome

Inherited LQTS is caused by the mutations of genes that encode a special class of proteins called ion channels, which are embedded on the surface (membrane) of muscle cells in the heart. Each ion channel has a tiny pore that can be open or closed. When the pore is open, some ions (sodium, calcium, or potassium, depending on the type of ion channels) may flow into and out of the cell. Because ions carry charges, their movement across cell membrane changes the electric potential of the heart cell membrane. This change is reflected in the EKG recording.

If an ion channel gene is mutated, the produced ion channel may not work properly. This may result in abnormal heart rhythm. At least nine genes are associated with LQTS. Their mutations result in different types of LQTS, referred to as LQT-1 to LQT-9 (see Appendix).

If you have LQT-1 and LQT-2, the flow of potassium ions through the ion channels in your heart cells isn't normal, which may cause problems when you exercise or when you're surprised or experience emotional stress. During these situations, you may develop a rapid and uncontrollable heart rhythm that may prevent your heart from pumping blood. This will result in death if it's not quickly brought under control. If you have LQT-3, the flow of sodium ions through ion channels in your heart cells isn't normal, which also may trigger a rapid and uncontrollable heart rhythm that can result in death. In LQT-3, problems usually develop when your heart beats slower than normal, such as during sleep.

Noninherited Long QT Syndrome

Acquired, or noninherited, LQTS may be brought on by certain medicines and other medical conditions. Presently, more than 50 medicines have been recognized to cause LQTS. Some of the commonly used medicines that may cause LQTS include:

  • Antihistamines and decongestants
  • Diuretics (pills that remove excess water from your body)
  • Antibiotics
  • Antidepressants
  • Cholesterol-lowering medicines and some diabetes medicines

Some people with medication-induced LQTS may also have an inherited form of the syndrome that doesn't cause symptoms unless they take certain medicines that lengthen the QT interval or lower potassium levels in the blood. This is sometimes called silent LQTS.

Other Causes of Acquired Long QT Syndrome

Excessive diarrhea or vomiting that causes a major loss of potassium or sodium ions from the bloodstream may cause LQTS. The syndrome lasts until the levels of these ions in the blood return to normal. The eating disorder anorexia nervosa and certain thyroid disorders may cause a drop in potassium ion levels in the blood, causing LQTS.

Appendix: Associated Genes

Type Gene Protein
LQT-1 KCNQ1 voltage gated K+ channel
LQT-2 KCNH2 voltage gated K+ channel
LQT-3 SCN5A voltage gated Na+ channel α subunit
LQT-4 ANK2 Ankyrin-B (Ankyrin 2)
LQT-5 KCNE1 voltage gated K+ channel
LQT-6 KCNE2 voltage gated K+ channel
LQT-7 KCNJ2 voltage gated K+ channel
LQT-8 CACNA1C voltage gated Ca2+ channel
LQT-9 CAV3 caveolin-3

The prolongation of the QT interval is due to slow repolarization of the membrane potential. Mutations in these K+ channels cause the loss of function, thereby reducing outward K+ current and consequently slowing repolarization. Mutations of the Na+ channel, SCN5A, cause incomplete inactivation, thereby increasing inward Na+ current which also slows repolarization (reference).

The protein ankyrin-B responsible for LQT-4 is not an ion channel. However, it is an adaptor protein that binds to sodium pump, sodium/calcium exchanger, and ion channels (reference 1, reference 2).

Caveolin-3 is the major component of a specific membrane domain (called caveolae) in the striated muscle. The SCN5A-encoded cardiac sodium channel localizes in caveolae. Mutations in the CAV3 gene are implicated in sudden infant death syndrome.