Short QT syndrome ... (Short QT syndrome) - Genes KCNH2, KCNJ2 and KCNQ1.

Short QT syndrome is an alteration of the normal heart rhythm (arrhythmia), in which the heart muscle takes less affected than usual to contract again. If left untreated, irregular contractions can cause various signs and symptoms, from dizziness and syncope, cardiac arrest, and sudden death.

Signs and symptoms of short QT syndrome, including sudden death, can occur at any time from early childhood to old age. 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. Others with short QT syndrome never develop symptoms.

The cause of this syndrome resides in mutations in KCNH2 genes (potassium voltage-gated cannel subfamily H, member 2), KCNJ2 (potassium voltage-gated cannel, KQT-like subfamily, member 1) and KCNQ1 (Potassium inwardly-rectifying cannel, subfamily J, member 2). KCNH2 gene, located on the long arm of chromosome 7 (7q36.1), belongs to the family of genes called KCN (potassium channels), along with the KCNJ2 gene, located on the long arm of chromosome 17 (17q24.3) and KCNQ1 gene, located on the short arm of chromosome 11 (11p15.5). These genes belong to the same family of genes and encoding proteins forming potassium channels in the cell membrane. These channels carry positively charged ions like potassium, inside and outside the cell, very important to generate and transmit electrical signals. In cardiac muscle, these ion channels play a critical role in maintaining the normal rhythm heart. Mutations in them increase the activity of the channels, which modifies the flow of potassium ions into cells, altering cardiac contractility, causing abnormal heart, rhythmic pattern of short QT syndrome. The specific role of potassium channel dependent on its protein components, and his physical location.

The channels in which the protein participates KNCH2 are active in cardiac muscle, which transport ions outside the cell. This form of ion transport is involved in reloading of the heart muscle after each contraction to maintain a steady pace. The KCNH2 protein is also present on nerve cells and some immune cells such as microglia in the central nervous system. This protein interacts with the KCNE2 protein to form the functional potassium channel. Four alpha subunits, encoded by the KCNH2 gene, form the channel structure. A beta subunit, encoded by the KCNE2 gene, binds to the channel and regulates its activity. In short QT syndrome, 2 mutations have been identified in the KCNH2 gene replacing specific amino acids in the protein KCNH2. This amino acid substitution alters the normal function of ion channels, increasing channel activity. By increasing the flow of potassium out of heart cells at a critical time during the heartbeat, this mutation is responsible for changes in heart rate own short QT syndrome. KCNH2 gene mutations have also been found in the Romano-Ward syndrome. There are some medications (antiarrhythmic, antimicrobials, ...) that may cause short - acquired QT syndrome, in which there is also cardiac arrest and sudden death.

Ion channels in which the protein participates KCNJ2 are present in skeletal and cardiac muscle cells, which transport ions into the cell. In skeletal muscle, these channels are involved in muscle contraction and relaxation, which enables movement. In the heart, the channels can charge cardiac muscle following each beat to maintain normal heart rhythm. In the formation of these channels plus the KCNJ2 protein, it is also necessary that the protein is PIP2 set. This activates the ion channel and helps stabilize protein in an open state, with which ions flow through the membrane. In short QT syndrome, they described at least two mutations that replace specific amino acids in the protein KCNJ2. This amino acid substitution alters the normal function of ion channels, increasing channel activity. Mutations in this gene are also responsible Andersen-Tawil syndrome and family atrial fibrillation.

KCNQ1 channels with protein are active in the inner ear and the heart muscle, which carry potassium ions outside the cell. In the inner ear helps maintain proper ions required for normal hearing. In the heart, the channels involved in recharging the heart muscle after each heartbeat to keep a regular rhythm. KCNQ1 protein is also produced in the kidney, lung, stomach and intestine where it is responsible for transporting molecules across the cell membrane. KCNQ1 protein interacts with the KCNE family proteins (such as KCNE1 protein) to form functional potassium channels. Four alpha subunits, each encoded by KCNQ1, form the structure of each channel. A beta subunit, encoded by the gene family KCNE, joins the channel to regulate its activity. It is thought that the molecule called PIP2 must bind to proteins consisting of KCNQ1 to function normally channels. PIP2 active ion channel and helps stabilize when open, which allows the flow of ions outside the cell. At least we have identified a mutation in people with short QT syndrome. This mutation replaces the amino acid valine for leucine at amino acid position 307 of the protein (Val307Leu or V307L). This amino acid substitution alters the normal function of ion channels, increasing channel activity. Besides the short QT syndrome, altering these proteins KCNQ1 channels found in: familiar atrial fibrillation; Jervell and Lange syndrome-Nielsen; Romano-Ward syndrome; Sudden death of childhood (SIDS) and acquired long QT syndrome syndrome.

Short QT syndrome is an autosomal dominant inheritance, so a single altered copy of the gene is sufficient to express the process. Some affected individuals have a family history of heart problems and sudden cardiac death. Other cases are sporadic and occur in people with no known history of this syndrome in your family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with short QT syndrome by complete PCR amplification of the exons of the KCNH2, KCNJ2 and KCNQ1 genes, respectively, and subsequent sequencing.

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).