Your genes control every aspect of the cardiovascular system, including the muscle contractions needed for your heart to beat, the strength of your blood vessels, and the structure of the chambers of your heart.
If a gene involved in the cardiovascular system contains a variant, this can interfere with its normal activity and cause symptoms – a heart condition. Heart conditions that are passed on through genes are known as inherited heart conditions. While common diseases like coronary artery disease can have a genetic component, this is usually in the form of multiple genetic variants each conferring a small increased risk. Inherited heart conditions are caused by one or a few variants that have big effects on health, and these conditions are much more rare.
Inherited heart conditions can be broadly grouped based on the area of the heart they affect. The role of the affected gene in the body determines the type of heart condition a person develops.
Structural heart conditions
These are problems with the structures that make up the heart – its muscles, vessels and valves. For example, cardiomyopathies are diseases of the heart muscle. The most common form, hypertrophic cardiomyopathy, affects up to 1 in 200 people. Hypertrophic cardiomyopathy causes a thickening of the heart muscle and subsequent narrowing of the chambers of the heart, which can make it harder for the heart to pump blood. The condition has variable penetrance, meaning that some people with hypertrophic cardiomyopathy will have no symptoms, while others will develop serious complications like heart failure or sudden death.
Variants in more than 13 genes have been linked with hypertrophic cardiomyopathy. The most commonly involved genes – MYH7, MYBPC3, TNNT2 and TNNI3 – encode proteins that form sarcomeres, the basic structural units that make up muscle tissue. Sarcomeres give structure to heart muscle, and regulate contractions. A variant in one of these genes may alter the structure of or reduce the amount of sarcomere proteins in the cell. However, it is not yet clear exactly how these changes to the sarcomere cause the symptoms of hypertrophic cardiomyopathy, or why some people are less affected than others.
Electrical heart conditions
Electrical heart conditions cause problems with the way the heart beats – known as arrhythmias – and are most often caused by changes in the structure or function of ion channels. These are proteins located in the cell membrane that control the transport of charged ions into and out of the cell. This movement of ions controls the beating of the heart – positive sodium ions enter the cell and create a depolarisation (a change in the overall charge of the cell) that causes the heart muscle to contract. Then, potassium channels open, positive ions move back out of the cell, and the cell begins to repolarise as it returns to its negatively charged resting state. This process repeats every time the heart beats.
Long QT syndrome is a condition that affects how long the repolarisation phase lasts – how long the heart takes to recharge after each heartbeat. It can be caused by variants in a number of genes, including KCNQ1, which encodes a potassium ion channel protein. More than 600 variants in KCNQ1 have been linked with long QT syndrome, and the functional effect of many of these is not known. Some variants alter the structure of the channel, while others produce a functioning channel that is degraded before it reaches the cell membrane. The result is a cell that is less effective at transporting potassium ions, which can increase the length of time that heart cells take to repolarise. In some cases, this can lead to ventricular fibrillation, a serious arrhythmia characterised by fast, chaotic heartbeats.
For more information and support for families affected by inherited heart conditions, visit the Australian Genetic Heart Disease Registry.