Extraordinary progress has been made in the field of molecular genetics over the past three decades. This has enabled scientists to not only identify the genes involved in the development of heart and lung diseases, but how they may progress and be treated best. In this article, we explore when you could consider a genetic test for your patient.
Genetics plays a key role in the development of many heart and lung conditions. In fact, 30-50 per cent of dilated cardiomyopathy cases – one of the main causes of heart failure in the young and reasons for needing a heart transplant – has a positive family history.
In addition, many heart and lung conditions are inherited in an ‘autosomal dominant’ pattern. This means that just one copy of the abnormal gene can cause the disease and each child of an affected carrier has a 50 per cent chance of inheriting the disorder.
Genetic tests may help identify diseases sooner than in traditional clinical practice. For example, primary ciliary dyskinesia (PCD) – an inherited disorder which can lead to irreversible lung deterioration – can be difficult to diagnose, taking up to 5.8 years on average. This is far longer than for another inherited lung condition, cystic fibrosis, which takes an average of 1.3 years to diagnose. If a genetic test is performed as soon as a clinician suspects PCD, this may help confirm a diagnosis sooner and inform a treatment strategy that will prevent much of the irreversible lung damage from occurring.
When to consider a genetic test
Clarify or confirm a diagnosis
If a patient has a heart or lung condition that is difficult to diagnose and/or is suspected to have an inherited or genetic component.
Identify the cause
If a heart or lung condition seems to recur in a family
Predict which family members are at risk
If a patient has a confirmed inherited heart or lung condition (positive genetic result), genetic testing may be extended to their family members, if appropriate.
Certain gene variants predispose to adverse drug effects, and so may influence treatment outcomes.
“Ideally, once a patient with the inherited disease – the ‘index’ patient – has a positive genetic result, it enables the age-appropriate testing of at-risk family members too,” explains Dr Deborah Morris-Rosendahl, head of the clinical genetics and genomics laboratory at RB&HH Specialist Care.
“By testing such family members and clinically monitoring those that have a positive genetic result, it allows us to capture and treat the inherited condition sooner to ensure the best patient outcomes. For example, in conditions like dilated cardiomyopathy, about 10 per cent of relatives with a positive genetic result already have evidence of left ventricular dysfunction even though they have no symptoms. Also, for severe, early-onset disorders, it is of great benefit for family planning, with the possibility of prenatal diagnosis.
“However, it is important to consider the implications of a genetic test. At Royal Brompton Hospital, we have a team of experienced clinical geneticists and genetics counsellors who will advise a referrer on each test to ensure it is right for their patient and their family members. They will also coordinate counselling, testing, screening, treatment and future monitoring at our hospital to ensure that every person tested is well informed and cared for.
“Also, we are extremely fortunate here. Whenever we get a positive genetic result for an inherited heart or lung condition, we can refer the patient to our colleagues who are some of the world’s best experts in each disease. There are very few places where a patient can be in such good hands.”
Cutting-edge genetic testing
Genetics testing at the Royal Brompton Hospital is a rigorous process conducted by an expert multi-disciplinary team. The newest, state-of-the-art next-generation sequencing technology is used to process and analyse samples for over 3000 patients a year – with the lab doubling its capacity each year in its continued drive for innovation, quality and efficiency.
“Determining a positive result isn’t easy. Most diseases are genetically heterogeneous and are caused by pathogenic variants in many different genes. Each of these genes harbours many variants that require filtering to arrive at the correct answer.
“This ensures that we are one of the quickest and most accurate centres in defining results,” explains Dr Morris- Rosendahl of her laboratory’s testing process.
“Also, genetics is a fast-evolving field – we are literally learning something new each day. We are constantly adapting to new research findings as well as contributing our own. Every time there is a new gene identified associated with a disease, we add it to our gene panel. This way, a patient can be assured that if their genetic result comes back negative, it is to the best of the world’s knowledge on clinical genetics at that point in time.”
“Improving technology is also aiding the identification of different types of genetic variation that can cause disease. This means that the current analysis is much more comprehensive than that previously possible. For example, we were recently able to identify a new intronic variant in the gene causing cystic fibrosis, which has finally provided a conclusive diagnosis for many adult patients and ended a lifelong diagnostic legacy.”
The laboratory at RB&HH Specialist Care is UKAS- accredited and actively participates in European MolecularGenetics Network (EMQN) and UK National External Quality Assessment (GenQA) schemes. It is responsible for all heart and lung genetic testing for London and South East England and accepts international and private referrals.
Genetic testing services available at RB&HH Specialist Care
Dr Deborah Morris-Rosendahl
Head of clinical genetics and genomics laboratory
Dr Morris-Rosendahl specialises in human molecular genetics and has published and lectured extensively on the genetics of cardiac, respiratory, neurological and other rare and complex diseases.