Sick sinus syndrome of ... (Sick sinus syndrome) - Genes SCN5A, MYH 6 and HCN4.
Sick sinus syndrome, also known as sinus node dysfunction, is a group of diseases related heart that may affect the heartbeat. "Sick Sinus" refers to the sinoatrial (SA) which generates electrical pulses beginning each heartbeat. These signals travel from the SA node to the rest of the heart, causing the heart muscle to contract and pump blood. In people with sick sinus syndrome, the SA node is not working properly. In some cases not produce adequate to trigger a regular heartbeat signals. In other cases , abnormalities disrupt the electrical impulses and prevent them from reaching the rest of the heart.
Signs and symptoms associated include bradycardia or tachycardia, although in some cases may occur bradycardia-tachycardia syndrome. Symptoms related to abnormal heartbeats may include dizziness, lightheadedness, syncope, palpitations, and confusion or memory problems. During the year, many affected people have chest pain, difficulty breathing or extreme tiredness. Usually, once symptoms appear sick sinus syndrome, they tend to worsen over time. However, some affected individuals fail to submit related health problems. Although the disease can be diagnosed in people of any age, most often affects older adults and increases coronary and vascular risk. These include atrial fibrillation, heart failure, heart failure and stroke.
Sick sinus syndrome may be due to genetic or environmental factors. In many cases, the cause of the disease is unknown. Although genetic changes are a rare cause of this disease, found mutations in two genes, SCN5A, located on the short arm of chromosome 3 (3p21) and HCN4, located in the long arm of chromosome 15 (15q24.1) responsible of the disease in a small number of families. These genes encode proteins called ion channels that transport ions in cardiac cells, including the cells that comprise the SA node. The flow of these ions is essential to generate electrical impulses that initiate each heartbeat and coordinate the heart muscle contraction.
They have identified at least 10 mutations in the SCN5A gene mutations to 5 HCN4 gene in people with sick sinus syndrome. These genetic changes lead to channel coding nonfunctional sodium channels or abnormal, that can not transport ions correctly. The flow of these ions is essential for the generation of electrical impulses that initiate each heartbeat and propagate these signals to other areas of the heart. The mutations reduce the flow of sodium ions, which alters the ability of the SA node to generate and disseminate electrical signals. These changes increase the risk of abnormally fast or slow heartbeat, which can cause dizziness, lightheadedness, syncope and related symptoms.
A particular variation in another gene, MYH6, located on the long arm of chromosome 14 (14q12), seems to increase risk of developing the disease. The protein encoded from MYH6 gene, part of the protein myosin, which generates the necessary mechanical strength for the heart muscle to contract. It is believed that genetic variation in MYH6 identified in the Icelandic population changes the structure of myosin. Specifically, this variation replaces the amino acid arginine by tryptophan at amino acid position 721 of the protein (Arg721Trp). The change can alter the structure of the heavy chain of myosin-? and interrupt their normal role in the contraction of heart muscle. These changes could alter the way in which the heart beats in some people, leading to bradycardia and related symptoms such as dizziness, lightheadedness and syncope.
More often, sick sinus syndrome is due to other factors that alter the structure or function of the SA node. These include a variety of cardiac disorders, other disorders such as muscular dystrophy, abnormal swelling, or hypoxia. Certain medications, including drugs administered to treat heart abnormal rhythms or high blood pressure, can alter the function of the SA node. One of the most common causes of sinus node disease in children is the trauma to the SA node, such as that caused during cardiac surgery procedures. In the elderly, sick sinus syndrome is often associated with age - related changes in the heart. Eventually, the SA node can harden and develop fibrosis, which prevents it from operating properly.
Most cases of this disease are not inherited. They described as sporadic, which means occurring in people with no history of disease in your family. When Sick sinus syndrome is due to mutations in the HCN4 gene it has an autosomal dominant inheritance, which means that a copy of the altered gene in each cell is sufficient to express the disease. In most cases, an affected person has a parent with the disease. Meanwhile, when the sick syndrome sinus is due to mutations in the SCN5A gene is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with sick syndrome sinus, by complete PCR amplification of the exons of SCN5A, MYH6 and HCN4 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).