Heart block progressive family (Progressive familial heart block) - Genes SCN5A and TRPM4.

Family progressive heart block is a genetic disorder that affects the heart normal heartbeat. The normal heartbeat is controlled by electrical impulses traveling through the heart of a coordinated manner. Heart block occurs when transmission power is blocked anywhere between the atria and ventricles. In affected individuals, the disease worsens with time: at the beginning of the disease, the electrical impulses are partially blocked, but eventually, these pulses are blocked completely inhibiting any signal through the heart. The partial heart block or bradycardia causes arrhythmia and can lead to fibrosis in the cells that transmit electrical impulses. Fibrosis contributes to the development of complete heart block, leading to an electrical signal without coordination between the atria and ventricles and inefficient pumping of blood in the heart. For its part, complete heart block can cause palpitations, shortness of breath, syncope or sudden cardiac arrest and death.

Family progressive heart block can be divided into types I and II. In turn, the type I is divided into types IA and IB. These types differ depending on where electrical transmission and genetic cause heart is interrupted. IA and IB in types, heart block originates from the branch, and type II, heart block originates from the atrioventricular node. Different types of family progressive heart block have similar signs and symptoms. Most cases of heart block are not genetic and not considered family progressive heart block. The most common cause of heart block is cardiac fibrosis, which occurs as a result of the normal aging process. Other causes of heart block may include the use of certain medications or an infection of the heart tissue.

Most cases of familial progressive heart block types IA and IB are due to mutations in SCN5A genes, located on the short arm of chromosome 3 (3p21) and TRPM4, located on the long arm of chromosome 19 (19q13.33) respectively. The proteins encoded from genes are these channels carrying cations between the inside and outside of cells. Both channels are abundant in cardiac cells and play a key role in the ability of these cells to generate and transmit electrical signals. These channels play an important role in signaling the start of each heartbeat, coordinating the contractions of the atria and ventricles, and maintaining a normal heart rhythm. In addition to the regulation of electrical signaling in the heart, the channel is TRPM4 important for the normal functioning of the immune system, nervous system, kidneys and pancreas.

They have identified several mutations in the SCN5A and TRPM4 family genes that lead to progressive heart block. Mutations in these genes change amino acids in the SCN5A protein and the TRPM4 channel, disrupting the normal function of the channel. As a result, cardiac cells have difficulties to produce and transmit the electrical signals that are required to coordinate normal heartbeat, leading to heart block. The death of these cardiac cells with disabilities over time can lead to fibrosis, worsening heart block. Mutations in other genes, some of which are unknown, representing the remaining cases of familial progressive heart block.

This disease is inherited as an autosomal dominant, which means that a copy of an altered gene in each cell is sufficient to express the disease. Some people with genetic mutations TRPM4 never develop the disease, a situation known as reduced penetrance. In most cases, an affected person has a parent with the disease.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with familial progressive heart block, by complete PCR amplification of the exons of SCN5A and TRPM4 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).