Cardiomyopathies are genetic conditions. The diagnosis of a genetic condition in an individual has implications for the other family members.
Hypertrophic cardiomyopathy is a familial disease in 90 per cent of cases, dilated cardiomyopathy is familial in 20 to 50 per cent of the cases and arrhythmogenic right ventricular cardiomyopathy is familial in more than 50 to 60 per cent of cases.
Genetic origin of the cardiomyopathies
The observation that hypertrophic cardiomyopathy runs in families led to the discovery that hypertrophic cardiomyopathy is a genetic condition. In 1989 the first mutation causing HCM was discovered. Since then most of the genes for the proteins responsible for the formation of muscle tissue have been found.
A similar model of research was applied to other cardiomyopathies, and during the last two decades several genes have been identified. This is the foundation of family screening principles.
Pattern of inheritance
The genetic conditions follow different patterns of inheritance. The information can be carried in the non sex chromosomes; that is the inheritance is not affected by gender. The information can be also carried only in the sex chromosomes; this is called linked to either the X or Y chromosome.
The main patterns of inheritance are dominant and recessive. Dominant is the genetic defect where only one copy of the defect is necessary to transmit the disease. Recessive conditions are those where two copies of the defective gene are necessary to cause the condition.
With a dominant condition only one of the parents needs to be affected and each of the descendants have a 50 per cent chance of inheriting the condition. With recessive conditions, both parents need to be affected and there is a 25 per cent chance of passing it on to each of the descendants.
Hypertrophic cardiomyopathy follows a dominant inheritance. Familial dilated cardiomyopathy also usually follows dominant inheritance, although recessive inheritance has also been described. Arrhythmogenic right ventricular cardiomyopathy can follow both patterns although the dominant trait is the more common.
The genotype is the genetic information in our genes. The phenotype is the expression of that information and its interaction with other factors like environment, education, food, etc.
Not all the genetic defects “written” in our genetic code express themselves ( affect us). Instead they depend on the penetrance of the defect and the interaction with other factors. This ultimately determines the phenotype, e.g. the development of cardiomyopathy.
The diagnosis of the cardiomyopathies is based on how the disease shows itself, ie in structural changes to the heart. The demonstration of a genetic diagnosis is not enough to diagnose the disease.
Medical aspects of family screening
A patient seeks medical attention when he or she perceives a health problem. The doctor asks what the problem is and then organises treatment to alleviate or cure the symptoms.
Screening is the practice of investigating apparently healthy individuals with the object of detecting unrecognised diseases, or people with an exceptionally high risk of developing disease, and of intervening in ways that will prevent the occurrence of disease or improve the prognosis when it develops.
In this relationship, the doctor or medical team are the ones asking the potential patient to seek medical attention. Screening is only applied when the benefits are greater than the potential harm the revealed information can have in an individual that perceives himself as healthy.
Family screening needs to be undertaken within a multidisciplinary team able to deliver appropriate information, support and medical attention.
The impact of the diagnosis or the possibility of transmitting a genetic defect to the next generation is great on the individual. It affects not only the individual now, but also the individual’s future and long-term health, capacity for work and every day issues such as driving. It is necessary to have in place a back-up support team for patient and relatives.
The cardiomyopathy units need to work together with the patient support groups. In this set-up the individual who is overwhelmed with the diagnosis of a genetic condition can find a group where similar needs can be identified, shared and supported.
Our society understands a family unit in very different arrangements. When a genetic condition is diagnosed the genetic family unit is that linked by blood. That link may not necessarily represent the current situation or might never have, such as in cases of adoption. The distance, communication, and longevity of different generations may sometimes make it difficult to complete the full family picture. Moreover, with regard to family screening, physicians can only advise. Anyone undergoing screening does so voluntarily.
All the information about a human being belongs to the individual. However with the genetic conditions the diagnosis has implications for other family members. The diagnosis of a dominant condition implies that the next generation has a 50 per cent chance of inheriting the condition. With a recessive disorder, the affected individual has two copies of the faulty gene, one from each parent.
Research and future perspectives
After several decades and continuous discoveries into the genetic code, there is still a long way to go. It is recognised that very often a cardiomyopathy is caused by a private mutation. That means a fault that is only recognised in that family or in a few others. While the recognition of the gene defects causing cardiomyopathies is greatly advanced we still lack a clear explanation of the ultimate causes of those diseases.
Active family screening is the more powerful tool for the development of a new line of research and disease understanding.
Sudden cardiac death
Family screening allows early diagnosis and prevention of sudden cardiac death. The identification of those individuals at risk can only be made if they are identified in time, while it is not too late. Effective therapy exits to prevent sudden cardiac death in individuals identified as being at high risk.