Dr. Perry Mark Elliott
Diseases of the heart and blood vessels are major contributors to human morbidity and mortality. A substantial proportion of cardiovascular disease is caused by genetic mechanisms and it is estimated that the total burden of inherited cardiovascular disorders is greater than most cancers. In recognition of the importance of genetics in cardiovascular disease, the ESC and the European Association of Human Genetics held their first joint symposium on the topic of genetic testing in cardiomyopathies. The aim was to provide practising cardiologists with an insight into the challenges that new knowledge and technologies pose for the diagnosis and management of patients with heart muscle disease.
In the first presentation, Dr Philippe Charron (Paris) presented a historical review of genetic testing in heart muscle disease, beginning with the discovery in 1990 of the first genetic mutation in hypertrophic cardiomyopathy by positional cloning, a technique used to subsequently identify the first ARVC related mutation in the rare syndromic form of ARVC–Naxos syndrome. Subsequent discoveries in all forms of cardiomyopathy have used a candidate gene approach and latterly next generation sequencing. The result of the past twenty years' endeavour is an astonishing diversity of genetic mutations in all forms of cardiomyopathy that challenges many of the assumptions about disease pathogenesis and suggests new therapeutic targets.
In the second presentation, Professor Jens Mogensen explored the reality of genotype-guided therapy. He highlighted the extreme and largely unexplained variability in phenotype expression observed in patients with identical mutations (even when they are part of the same family), which continues to limit the role of genetic data in treatment. Nevertheless, he also demonstrated that identification of clearly pathogenic mutations can be used in the management of families through predictive testing and gave some examples of genetic mutations that are associated with highly penetrant and malignant phenotypes (e.g. Lamin AC) that, when identified, can alter therapy.
Dr Fokstuen (Geneva, Switzerland) then presented a very clear overview of the pros and cons of new high throughput genetic screening technologies. She demonstrated the dramatic impact that these have had on the ability to screen large numbers of genes at relatively low cost. While this has resulted in a dramatic increase in the efficiency of genetic screening in the clinical setting, she cautioned the audience about some important limitations of the techniques and the new ethical and legal challenges posed by genotyping on a whole exome or genome scale.
Dr Christiaans (NL) then moved on to a very thoughtful overview of the principles and practice of genetic counselling in the setting of cardiomyopathy clinics. She explained the differences between different forms of counselling and emphasised the multidisciplinary approach essential in the effective delivery of genetic testing to patients and equally important, families. She drew the audience’s attention to the fact that the principles and consequences of genetic counselling apply equally to clinical testing.
Finally, Professor McKeown (Great Britain) presented a comprehensive review of the clinical service models for cardiogenetic services that are being discussed in different European countries. He explored the current situation of fragmented and poorly planned services and examined the implications of various national guidelines for the provision of coordinated expert teams. While accepting that there is no one model that fits every healthcare system in Europe, he did emphasise the fact that multidisciplinary working and coordinated networks are the goal for most countries.
When taken as a whole, this session provided the audience with a thorough overview of the role of genetics in the management of patients with inherited cardiomyopathies. The probing questions and positive feedback from the audience suggest that this will not be the last joint genetic symposium at the ESC congress.
Genetic testing for cardiomyopathies in clinical practice
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