Cardiomyopathies, or heart muscle diseases, are a common cause of heart failure, which is a leading cause of death in most societies.
There are several different types of cardiomyopathy, many of which can have a hereditary cause. The two major types of cardiomyopathy are dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM).
Many different genetic causes of cardiomyopathy have been discovered and identifying the underlying genetic cause can influence medical management decisions and preventive screening options for at-risk relatives.
Careful consideration of the personal and family history should be given when deciding which cardiomyopathy panel is most appropriate for testing in an individual patient or family.
Cardiac arrhythmias on the other hand also constitute a main cause of morbidity and mortality. Congenital cardiac arrhythmias are a separate group of heart disorders resulting from defects in the electro-physiological properties of the heart.
Specifically, coordination of cardiac activity includes, among other, the synchronous and sequential opening and closing of ion channels in response to the electrical potential and subsequent transmission of the action potential to each compartment of the heart.
For example, sudden cardiac death (SDC) is a key cause of mortality, affecting all ages. The primary cause of sudden cardiac death in individuals older than 45 years is atherosclerotic coronary artery disease. However, in individuals <45 years, genetic and hereditary defects in specific genes are associated with the condition in up to 80% of the families.
The most common types in young people include cardiomyopathies (e.g. hypertrophic cardiomyopathy) and electrophysiology abnormalities (e.g. Long-QT syndromes).
Determining the genetic cause of cardiomyopathies can be complex. There have been many different genes and many different mutations involved in inherited predisposition to cardiomyopathy.
The genetic cause is further complicated because there is significant phenotypic overlap between the different types of cardiomyopathy and also significant overlap in the genetic causes between subtypes.
For example, at least 19 genes have been implicated in both HCM and DCM, and occasionally a person who initially had HCM, may not be diagnosed with heart disease until the disease is very advanced and presents as DCM.
Although environmental factors clearly contribute to arrhythmogenesis, family and population studies have also demonstrated an underlying genetic etiology.
For example, mutations in >20 genes, which encode and/or modulate specific ion-channels, are associated with various forms of arrhythmias, occurring in an otherwise structurally normal heart. As an example, Brugada Syndrome (BRS), is associated with mutations in at least seven different genes and is characterized by an increased risk of fatal ventricular arrhythmias.
Another example of such a disease are the Short QT (SQTS) and Long QT (LQTS) syndromes, associated with mutations in approximately 12 different genes that code for ion channels and are characterized by an increased risk of possibly fatal arrhythmias.
Generally, the majority of cardiogenetic diseases are expressed and inherited in an autosomal dominant manner, which means that individuals with a mutation in only one of the two copies of a gene have a particularly high risk of manifesting the disease and all first-degree relatives of a patient have a 50% risk of inheriting the disease. It is also important to bear in mind that different mutations in the same gene can lead to the expression of different types of a cardiogenetic disease.
Previous genetic testing options for cardiogenetic disorders and arrhythmias were extremely slow (months or years) and incomplete (testing of only a few genes) and as a result the underlying genetic causes-gene mutations were not revealed in patients and relatives with hereditary heart diseases.
To the extent, therefore, that until now genetic testing was selective, incomplete and often expensive, parallel analysis of all known genes through genomic testing affords successful and final diagnosis in a single step.
The identification of the pathogenic mutation is important for genetic counseling of patients and families, for facilitating timely diagnosis in individuals at risk.
Moreover, in many cases the exact knowledge of the genetic cause may lead to a much more effective management of the symptoms and to determine the appropriate individualized medication or treatment.