SNP Shot: Genomic Insights

Progressive familial heart block is an inherited condition that disrupts the heart's natural rhythm. A healthy heartbeat relies on a precise electrical system. This system begins in the sinoatrial (SA) node, the heart's natural pacemaker, located in the upper chambers (atria). The SA node generates electrical signals that travel to the atrioventricular (AV) node. From there, the signals pass to the bundle of His, which divides into smaller branches called bundle branches. These branches carry the electrical signals to the lower chambers (ventricles), triggering them to contract slightly after the atria, creating a normal heartbeat.

Heart block occurs when the electrical signals are impeded at any point between the atria and ventricles. In progressive familial heart block, this blockage worsens over time. Initially, the signals are only partially blocked, leading to slow or irregular heartbeats (bradycardia or arrhythmia) and potential scar tissue (fibrosis) development in the electrical pathways. This fibrosis can lead to complete heart block, where no signals pass between the atria and ventricles, resulting in uncoordinated heart activity and inefficient blood pumping. Complete heart block can cause palpitations, shortness of breath, fainting (syncope), or even sudden cardiac arrest and death.

Progressive familial heart block is categorized into type I (further divided into IA and IB) and type II, based on the location of the electrical interruption and the underlying genetic cause. In types IA and IB, the blockage is located in the bundle branches, while in type II, it occurs in the AV node. Despite the different locations, the various types share similar symptoms.

Most cases of heart block are not inherited and are not considered progressive familial heart block. The most frequent cause of heart block is age-related fibrosis of the heart. Other causes include certain medications or heart tissue infections.

Inheritance:

Progressive familial heart block types I and II follow an autosomal dominant inheritance pattern. This means that inheriting just one copy of the mutated gene is enough to cause the condition. However, some individuals with TRPM4 gene mutations may never develop the condition, a phenomenon known as reduced penetrance. Typically, an affected individual has one parent who also has progressive familial heart block.