Inherited Heart Diseases are a group of heart diseases caused by genetic abnormalities that run in families and often go unnoticed until someone develops unexplained heart failure, life-threatening arrhythmias or sudden cardiac death. The prevalence of inherited heart diseases ranges from 1 in 200 to 10000 in the general population. Unraveling the mysteries in our genetic code that have been implicated in young sudden deaths has been the focus of the multidisciplinary cardio-genetic teams that have been established across the globe in the recent past.
With the sequencing of the human genome at the turn of the 21st century arrived the era of human genomics, which has revolutionized the clinical application of the genetic testing modality. What was until then a research tool confined to the laboratory was catapulted to the clinic and the forefront of disease management as a diagnostic, prognostic and therapeutic tool. The advances in human genetics have aided in successfully identifying the causative genes for a range of cardiac disorders, particularly inherited heart diseases or inherited cardiac conditions (1).
The double-stranded human genome of each cell contains 6.4 billion nucleotides. The approach to identifying the causal genes and variants of heart diseases has evolved dramatically over the past 3 decades. The conventional approach of genetic linkage analysis in large families, which was very successful in linking causal DNA mutations to rare single gene disorders, has all but been replaced with the newer approaches of next-generation DNA sequencing (NGS) in small families and individual cases and genome-wide association studies (GWAS) in large populations. The newer approaches have not only expanded the applicability of the genetic tool in everyday patient care but have also become much more affordable for the common man.
Among the different types of heart diseases like coronary heart disease, congenital heart disease, valvular heart disease and inherited heart disease, the last group contributes to the largest proportion of sudden cardiac death in apparently healthy individuals below the age of 45 years. Cardiomyopathies and channelopathies are the two major types of inherited heart diseases of which a wealth of causative genetic information has become available since the first hypertrophic cardiomyopathy gene MYH7 was discovered in 1989 (2).
Inherited cardiomyopathies, where the affected individuals have structural and functional abnormalities of the heart due to an underlying gene mutation, are estimated to affect up to 1 in 500 individuals. The following are the genes implicated in the 4 main types of cardiomyopathies.
Channelopathies or inherited arrhythmias, where individuals with a structurally normal heart have an abnormal heart rhythm due to an underlying gene mutation, are the leading cause of sudden arrhythmic death syndrome (SADS). The diseases in this group are:
Other inherited conditions that can affect the heart are:
A wide range of symptoms, from an absence of symptoms to fatal cardiac events, is known in individuals with inherited heart diseases. The following symptoms should alert the physician:
As arrhythmias can be triggered by exercise, athletes are particularly prone to developing symptoms during or after training. Sports cardiology is the field of medicine that helps screen athletes for inherited conditions and manages them appropriately. The below diagram shows some common presentations in individuals with inherited arrhythmias or channelopathies.
Clinical presentation of inherited arrhythmias
Inherited heart diseases often pose a diagnostic dilemma, even to the best of the clinical minds. Misdiagnosis and delayed diagnosis are extremely common. The first step in diagnosing an inherited heart disease is taking a detailed history of the patient’s symptoms. Understanding the family history thoroughly, especially eliciting a three-generational history gives a clear picture of the disease pattern in the family members. The following tests are then performed to throw light on the electrical activity, structural pattern, and functional aspects of the heart.
The diagnostic tests used in Inherited heart disease patients
Genetic testing is the process of taking a sample of a person’s DNA to look for changes that could cause inherited heart disease. It is performed like a routine blood test but involves the comprehensive analysis and interpretation of the genetic data and provides valuable insights into the genetic abnormalities that are known to cause heart diseases. Cardiac genetic testing is best undertaken in a specialized multidisciplinary healthcare setting where specific clinical and genetic expertise is available (3).
Genetic testing can be used to:
The above tests are first performed on the proband (the first family member to show symptoms) and then on the family members to identify the affected individuals and treat them early to prevent life-threatening arrhythmias and sudden death.
The time taken for genetic test results to become available is around 4-6 weeks. Genetic counseling is provided before performing the genetic test and after the test results become available so that the tested persons understand the implications of the test and the results.
To manage inherited heart disease, one or more of the following modalities may be employed. The choice of treatment is based on the symptom profile and the risk of sudden death in the affected individual.
The establishment of multidisciplinary teams is vital to the systematic care and follow-up of families with inherited heart diseases. A host of healthcare professionals and support staff as shown in the figure below have to work in unison to achieve the common goal of preventing sudden death due to cardiac genetic abnormalities.
Specialists constituting an inherited heart disease clinic
Dr. Priya Chockalingam MBBS, MRCPCH, Ph.D.Cardiogenetics Clinical Lead & Consultant Inherited Heart Diseases Kauvery Hospital Chennai
