The role of the GP in genomic medicine
The term ‘genomic medicine’ encompasses both genetics and genomics. While genetics focuses on the DNA coding for single functional genes, genomics is the study of the entirety of an individual’s DNA. Genomic medicine involves using genomic information about an individual as part of their clinical care (for example, for diagnostic or therapeutic decision-making).
The term 'precision medicine' refers to the use of genomic information alongside other individual and environmental factors to refine disease prediction, prevention and treatment. Genomic information about how an individual’s genes influence their response to drugs (pharmacogenomics) may inform personalised medical management through the stratified use of medicines.
As access to genomic testing increases – either through research programmes, as part of clinical care or by direct-to-consumer testing from commercial companies – patients and their relatives will turn to their GP for discussion and advice, and GPs must be aware of the implications of this.
As a GP your role is to:
- take and consider family histories to identify families with, or at risk of, genetic conditions (including autosomal and X-linked disorders) and familial clusters of common conditions such as cancer, cardiovascular disease and diabetes
- identify patients and families who would benefit from being referred to appropriate specialist services
- manage the day-to-day care of patients with genetic conditions, even if the patient is under specialist care
- coordinate care across services, including transitions from paediatric to adult services
- communicate information about genetics and genomics, including discussing results from antenatal and newborn screening programmes
- understand how genomic information is used within the context of routine clinical practice.
Knowledge and skills guide
For each problem or disease, consider the following areas within the general context of primary care:
- the natural history of the condition, including whether acute or chronic
- the incidence and prevalence, including in different demographic groups
- typical and atypical presentations
- recognition of normal variations throughout life
- risk factors, including lifestyle, socio-economic and genetic factors
- diagnostic features and differential diagnosis
- recognition of 'alarm' or 'red flag' features
- appropriate and relevant investigations
- interpretation of test results
- management, including initial and continuing care, chronic disease monitoring, emergency care and end-of-life care
- patient and carer information and education, including self-care prognosis.
Common and important conditions
Variations in the human genome may have no effect, predispose to common diseases or result in genetic conditions. Many of these conditions (for example, cystic fibrosis and Huntington’s disease) are individually rare, but as a group share common principles in terms of diagnosis, management and supporting patients and their families. As a GP you should understand the following:
- autosomal dominant conditions (for example, familial hypercholesterolaemia, polycystic kidney disease, Huntington's disease, thrombophilias)
- chromosomal disorders (for example, Down’s syndrome, trisomy 18, Turner syndrome, Klinefelte’sr syndrome)
- autosomal recessive conditions (for example, cystic fibrosis, hereditary haemochromatosis, haemoglobinopathies)
- X-linked disorders (for example, Fragile X syndrome, Duchenne muscular dystrophy and Becker muscular dystrophy, haemophilia).
Many common conditions follow a multifactorial inheritance pattern, for example, ischaemic heart disease, hypertension, diabetes, cancer and obesity. Some patients with a common condition demonstrate familial clustering of the condition or have an autosomal dominant condition that confers high risk, for example, BRCA1 pathogenic variant in breast cancer, Lynch syndrome or familial hypercholesterolaemia in ischaemic heart disease.
Symptoms, signs and modes of presentation
Most variations in the genome are asymptomatic. In patients who have, or are at risk of developing, a genetic condition, consider the following:
- clinical suggestion of inherited disease (for example, multiple family members affected at a younger age)
- genetic 'red flags' (for example, recurrent miscarriage, developmental delay in conjunction with other morbidities)
- predisposition to common diseases (such as coronary artery disease or cancer)
- symptoms and signs of specific conditions (see 'Common and important conditions' above)
- symptom complexes and multisystem involvement
- variability of symptoms and signs between family members for some genetic conditions, particularly some autosomal dominant conditions (such as neurofibromatosis type 1), which may be due to variable penetrance, expression or anticipation.
Assessing genetic risk
- How to take a family history (relevant questions, interpretation, how to draw a pedigree)
- Basic inheritance patterns (autosomal dominant and recessive, X-linked, mitochondrial, multifactorial)
- Principles of assessing genetic risk, including:
- principles of risk estimates for family members of patients with single gene disorders
- principles of recurrence risks for simple chromosome anomalies (for example, trisomies)
- contribution of susceptibility variants to risk of common chronic conditions and infectious diseases such as Covid-19
- use of information about genetic susceptibility to common conditions to aid stratification into risk categories (polygenic risk scoring)
- conversations around risk in the context of antenatal screening
- online risk assessment tools, as they become available
- other factors contributing to genetic risk (for example, ethnicity, effects of consanguinity)
Investigations
- Genetic and genomic tests (diagnostic, predictive, carrier testing) and their limitations
- Diagnostic tests in primary care (for example, cholesterol, ultrasound for polycystic kidney disease, testing for hereditary haemochromatosis)
- Carrier testing for families with autosomal recessive conditions such as sickle cell, thalassaemia or cystic fibrosis
- Antenatal and newborn screening programmes (for example, Down’s syndrome, cystic fibrosis, sickle cell and thalassaemia)
Service issues
- Systems for following up patients who have, or are at risk of having, a genetic condition and have chosen to undergo regular surveillance (for example, imaging for breast cancer and adult polycystic kidney disease or endoscopy for colon cancer)
- Eligibility and referral pathways for NHS genetic and genomic testing
- Services and support available for those with an inherited condition (including genetics and genomics medicine services)
- Local and national guidelines (for example, for a family history of certain cancers)
Additional important content
- Genomic nomenclature (for example, what is meant by non-coding DNA, susceptibility variant, pathogenic variant and variant of unknown significance (VUS))
- Difficulties in determining the exact genomic cause of a condition (for example, a learning disability)
- Heterogeneity in genetic diseases
- Skills in communicating genetic and genomic information, taking into account a person’s health literacy
- Skills and techniques for non-directive, non-judgmental discussion about genetic conditions, taking into account an individual's ethnic, cultural and religious context and their beliefs
- Spectrum of risk-reducing measures, from lifestyle modification to targeted treatments for certain conditions (for example, mastectomy and/or oophorectomy for BRCA1/2 mutation carriers, colectomy for adenomatous polyposis coli (APC) mutation carriers, aspirin for Lynch syndrome, statins for familial hypercholesterolaemia, venesection for haemochromatosis, losartan for patients with Marfan syndrome), targeted gene therapies
- Reproductive options available to those with a known genetic condition (for example, having no children, adoption, gamete donation, prenatal diagnosis, neonatal screening or testing)
- Emotional, psychological and social impact of a genetic diagnosis on a patient and their family
- Clinical and ethical implications for family members of an affected individual, depending on the mode of inheritance of a condition (autosomal dominant, recessive and X-linked single gene inheritance; de novo and inherited chromosomal anomalies; mitochondrial inheritance and somatic mutation)
- Ethical issues surrounding:
- confidentiality and non-disclosure of genetic information within families (particularly when information received from or about one individual can be used in a predictive manner for another family member in the same practice)
- genetic testing (for example, testing in children, presymptomatic testing)
- the 'right not to know'
- the use of information (for example, for insurance or employment issues)
- Pharmacogenomics: the role of genomic information in prescribing.
Case discussion
Emily Russo, a healthy 37-year-old woman, presents to you with concerns about developing cancer because her mother was diagnosed with breast cancer at the age of 38 and died at the age of 40. Her maternal grandmother had also died from cancer in her late 40s, and her cousin, Lisa Parker, who is 42 years old, has recently been diagnosed with ovarian cancer.
Emily is referred to the local clinical genetics service, where she sees a genetic counsellor who explains that the family pattern could be consistent with one of the family cancer syndromes. The genetic counsellor explains that it would be helpful to find out more information from her cousin. On further discussion with her family, Emily finds that her cousin had a genetic test at the time of her ovarian cancer diagnosis, which showed a BRCA 1 pathogenic variant.
Emily sees the genetics service again to discuss being tested to see if she has also inherited the pathogenic variant. She is considering IVF (in vitro fertilisation) with her female partner and wants to know if the genetic testing may be helpful in informing decisions in this regard.
Questions
These questions are provided to prompt you to consider the key points of the case. They can form the basis for a case discussion with your educational supervisor and will assist you in writing reflective entries in your ePortfolio. The questions are examples to trigger reflection and are not intended to be comprehensive.
| Core capabilities | Questions |
|---|---|
Fitness to practise This is about professionalism and the actions expected to protect people from harm. This includes the awareness of when an individual’s performance, conduct or health, or that of others, might put patients, themselves or their colleagues at risk. | How do my own views influence the way I communicate information about genetic and genomic tests and results, in particular those that may impact on the wider family? What are the limits of my competence in this case? |
An ethical approach This is about practicing ethically with integrity and respect for equality and diversity. | What potential ethical dilemmas could such a case present, and how would I address them? What are the ethical implications of consulting with and providing care for family members of an individual in whom a genetic diagnosis has been made? What are my thoughts and feelings about private companies offering genetic tests for the general public? |
Communicating and consulting This is about communication with patients, the use of recognised consultation techniques, establishing and maintaining patient partnerships, managing challenging consultations, third-party consulting, the use of interpreters and consulting modalities across the range of in-person and remote methods. | How can I communicate the risks of common patterns of genetic inheritance using simple language? What do I need to consider when communicating information relating to a genetic disorder? |
Data gathering and interpretation This is about the gathering, interpretation and use of data for clinical judgement, including information gathered from the history, clinical records, examination and investigations. | What tools are available to GPs for recognising and stratifying patients who may have an inherited predisposition to developing cancers? How can I recognise individuals or families at the greatest risk of having genetic conditions? What clinical information does my local specialist genetics service require prior to referral? |
Clinical examination and procedural skills This is about clinical examination and procedural skills. By the end of training, the GP registrar must have demonstrated competence in general and systemic examinations of all the clinical curriculum areas, including the five mandatory examinations and a range of skills relevant to general practice. | Are there any clinical examinations I would wish to perform in this case? Would the findings affect my decision to refer (and to whom)? |
Decision-making and diagnosis This is about having a conscious, organised approach to making diagnosis and decisions that are tailored to the particular circumstances in which they are required. | What are the best ways of taking, recording and interpreting a genetic family history? When am I likely to refer patients to secondary care? |
Clinical management This is about the recognition and a generalist’s management of patients’ problems. | If Emily is found not to have inherited the BRCA1 gene, does this mean she will not develop breast or ovarian cancer? What guidelines exist to guide my management of people with genetic conditions? How do I access them? Do I know when and where to seek timely and reliable advice on genetic and genomic issues or queries (for example, about inherited disorders or testing)? |
Medical complexity This is about aspects of care beyond the acute problem, including the management of comorbidity, uncertainty, risk and health promotion. | What roles could the GP play in managing complexity in this case? What other sources of advice and support are available to GPs? What is the role of pharmacogenomics in current and future prescribing practice? |
Team working This is about working effectively with others to ensure good patient care and includes sharing information with colleagues and using the skills of a multiprofessional team. | How can GPs work with local genetics departments to facilitate a seamless two-way transfer of information? How can the practice work as a team to ensure that patients with an identified predisposition to cancer or other genetic conditions are not lost to follow-up? |
Performance, learning and teaching This is about maintaining the performance and effective CPD of oneself and others. The evidence for these activities should be shared in a timely manner within the portfolio. | How can I ensure that information for my patients about the availability of genetic or genomic tests and targeted management is up to date? How do I keep myself updated about new developments in genetics, genomics and testing? |
Organisation, management and leadership This is about understanding how primary care is organised within the NHS, how teams are managed and the development of clinical leadership skills. | What codes within my electronic medical record system can I use to record a family history of cancers or any other genetic disorder? What systems are in place to record that someone has had a genomic test? What systems are in place to follow up patients who have, or are at risk of, a genetic disorder and have chosen to undergo regular surveillance? |
Holistic practice, health promotion and safeguarding This is about the ability of the doctor to operate in physical, psychological, socio-economic and cultural dimensions. The doctor is able to take into account the patient’s feelings and opinions. The doctor encourages health improvement, self-management, preventative medicine and shared care planning with patients and their carers. The doctor has the skills and knowledge to consider and take appropriate safeguarding actions. | How might a patient's cultural and religious background, and beliefs concerning genetics, genomics and inheritance, impact on the consultation? What range of feelings might a person have after finding out they have, or have not, inherited a predisposition to a condition? What population screening programmes should Emily continue to participate in? |
Community health and environmental sustainability This is about the management of the health and social care of the practice population and local community. It incorporates an understanding of the interconnectedness of health of populations and the planet. | How would the views of the local community towards genetics, genomics and screening impact on the ways in which the family are likely to take up services? How might the make-up of the local population affect the prevalence of genetic conditions and attitudes towards genetic disease? Where are my local genetic or genomic departments and are there any agreed local protocols for referrals? |
How to learn this area of practice
Work-based learning
Primary care is a good setting to learn about genomic medicine because of the family-based focus and opportunities for staged counselling. Learning opportunities include how to recognise conditions with a genetic component; how to appropriately manage genetic implications for the individual and family, particularly where there are ethical, social and legal issues; and when and how to refer patients to specialist services. As many common conditions seen in general practice (including cancer, diabetes and heart disease) are multifactorial with a genetic component, managing them can also help develop awareness of how genomics affects disease.
Many hospital specialties, such as fetal medicine, paediatrics and some adult medical and surgical specialties, will be requesting genomic tests. As a GP registrar, you can build your knowledge and awareness of genomic issues through observation and practice in these settings.
You may wish to shadow allied health professionals who have a role in genomic medicine. This might include, for example, pharmacists managing lipid optimisation (identifying those who may have familial hypercholesterolaemia) and pharmacogenomics in other specialties, such as targeted therapies in oncology, and family history breast care nurses in surgery.
GP registrars with an interest in genomic medicine may also wish to take the opportunity to learn from consultant geneticists, genetic counsellors and other relevant allied staff such as genomic associates and family history administrators working in regional specialist genetics or genomics services. Learning may include developing your understanding of the genetic counselling process, diagnosis and management of genetic conditions, and reproductive options, including prenatal diagnosis for at-risk couples.
Self-directed learning
The RCGP Genomics toolkit has a collection of resources, including training materials, audit suggestions and links to relevant clinical guidance and patient information.
The NHS England Genomics Education Programme website includes information about taking and drawing a family history, core concepts in genomics, genetic conditions and genomic terminology.
The British Society for Genetic Medicine website contains links to regional genetic centres, which often have information on referral pathways and criteria.
You can find an e-Learning module(s) relevant to this topic guide at elearning for healthcare.
Examples of how this area of practice may be tested in the MRCGP
Applied Knowledge Test (AKT)
- Knowledge of antenatal and newborn screening programmes
- Consent, capacity and confidentiality of genetic testing
- Interpretation of a pedigree analysis chart
Simulated Consultation Assessment (SCA)
- A woman with one affected sibling requests genetic screening for breast cancer
- A woman attends for preconceptual advice because her nephew has Duchenne muscular dystrophy
- A neurology letter (provided) states 'symptoms suggest cerebellar ataxia, with autosomal recessive inheritance'. The patient attends to discuss the implications of her own probable diagnosis for her children.
Workplace-based Assessment (WPBA)
- Audio Consultation Observation Tool (Audio COT) with a parent discussing the chances of passing his thalassemia-associated variant (trait) to his children
- Log entry about communicating with an adult patient who has Down’s syndrome
- Log entry about a mother who is finding it hard to cope with her child having cystic fibrosis