Abstract
Introduction
Several prominent reports and publications have highlighted the need for mainstream medical specialties to acquire knowledge and skills in genetic medicine and incorporate genetics into their practice. 1–3 Good communication between clinical genetic services and mainstream specialties will be required as well as inclusion of genetic training in the continuing professional development of mainstream specialties. Here we describe a real but anonymous case history that highlights the need for such integration to receive prompt and appropriate attention.
Case report
A 57-year-old woman, June, was referred to the regional genetics service by her general practitioner to discuss her own and her family's history of cancer. June had developed endometrial cancer at the age of 46 and three years later a separate right-sided colonic cancer had been diagnosed. June's father had also had a colorectal cancer in his 50s, as had a paternal uncle. The family history was therefore suggestive of an inherited genetic predisposition to colorectal/endometrial cancer, known as Lynch syndrome or hereditary non-polyposis colon cancer (HNPCC). June provided consent for genetic testing so that other family members could be informed of their risks. Detailed analysis of the MLH1, MSH2, MSH6 and PMS2 genes revealed a pathogenic MSH2 mutation characteristic of HNPCC. The condition is inherited in an autosomal-dominant fashion, so each of June's three children has a 50% chance that they have inherited the cancer predisposition from her.
A person who has inherited such a mutation has a lifetime risk of developing colorectal cancer of around 80% compared with the population lifetime risk of around 5%. Women also have an increased lifetime risk of developing endometrial cancer, which is about 50% compared with the population risk of about 2%. There are also other smaller increased risks of cancer. Once an inherited mutation has been identified in an affected person, other family members can be offered a predictive genetic test to see whether they too have inherited the cancer predisposition. Knowing who is at risk can allow targeted organ surveillance. Two-yearly colonoscopy has been shown to improve the detection of early or precancers in such individuals, thus improving their survival rate. 4
Once the inherited MSH2 mutation had been identified in June, she was provided with information and letters to pass on to her close relatives, including her three children.
Sometime later, one of June's sons, Gary, was referred to the same genetic service for a discussion on her family history. The referral letter stated that Gary, 29, did not, at this stage, want genetic testing as he was going through a difficult time and wanted to defer the discovery of such significant and irreversible information until a later stage. Gary's general practitioner had also referred him to colorectal services for surveillance on the basis of his family history, since an elevated risk could not be excluded. Gary was offered a genetic clinic appointment to discuss future testing, other cancer risks and surveillance options; however, he failed to attend that appointment. The nurse counsellor then contacted Gary by telephone and was surprised to hear that Gary's colorectal surgeon had already organized genetic testing. Gary had been told that the result was negative, and therefore he had not seen the need to attend the genetics clinic appointment. Since predictive genetic testing for HNPCC is currently usually done through regional genetics services, the laboratory was contacted to see when such testing had taken place and who had authorized it. The laboratory confirmed that they had not done any HNPCC genetic testing on a blood sample from Gary.
Further discussion with Gary revealed that when he had seen the colorectal surgeon he had been told that it would be necessary to have a genetic test before any colonoscopy surveillance could take place. Although he had not wanted a genetic test, when presented as a prerequisite to surveillance he had agreed, and a sample of his blood was taken for DNA extraction and genetic testing. Some weeks later he was told by the colorectal team that his genetic test was negative and that he therefore did not need colorectal surveillance.
On discussion with the genetics laboratory it was found that the gastroenterology service had indeed requested genetic testing. However, under clinical details, the request card stated ‘family history of HSMN’ and they had requested HSMN gene testing, not hMSH2, the gene that had been found to be abnormal in Gary's mother. HSMN, or hereditary motor and sensory neuropathy – also known as Charcot Marie tooth disease – is also an inherited condition but one that affects the neuromuscular system and not one Gary was at increased risk of. As a result, Gary was falsely reassured by the wrong negative test results.
Discussion
The range of conditions for which genetic testing is possible has expanded exponentially over the last two decades. Initially genetic testing could at best clarify risks of future disease or of reproductive risks, but recently more and more tests have been introduced into NHS services where clinical management can be altered as a result of the test. The increase in the number of tests with clinical utility has led to several calls for ‘mainstreaming’ genetic services. 3 In part this is in recognition of the fact that the relatively small specialty of clinical genetics cannot expand quickly enough to deal with this increase in demand for genetic testing, but also that such testing will become integral to the management of conditions in other specialties. There have therefore been calls for improved education in genetics in mainstream specialties as well as improved liaison activities with regional clinical genetics services. 5 There is a risk, however, that the complexities of genetic medicine are lost if this mainstreaming happens too quickly and without appropriate educational activities. It is tempting to view a genetic test much like any other blood test, which can be requested as part of a panel of investigations. In doing so, the subtleties surrounding consent to a test with potential major and long-term medical consequences for the patient and their relatives may be lost.
Genetic professionals are committed to the idea that genetic testing should not be performed without adequate consent and that genetic information should be disclosed in ways that are appropriate and supportive. They are trained to provide appropriate care and information to the patient referred to them but, depending on the circumstances, they may also have a duty of care for that patient's relatives. One person's result may be relevant to several family members, and appropriate communication with these relatives is more complex than just telling them they should have a test. Taking consent seriously means that a decision to decline or defer a genetic test should be respected, even if this will result in greater uncertainty about what risks that person might be at. Perhaps because genetic practice initially offered few medical interventions as a result of a test, clinical genetic practice accepts that patients may not wish to have a genetic test even if an accurate test is available to them. The focus of discussions about genetic testing is more about supporting the patient's own decision-making process with sufficient information, than about achieving any particular outcome.
Although genetic tests are not fundamentally different from any other type of medical test, the potential for discrimination, guilt or stigma means that some people will want to consider carefully whether or not to test. At the same time, colonoscopy surveillance is not without risk and if Gary's risk was not increased he could be spared this investigation. This may have prompted the gastroenterology team to offer surveillance conditional upon a test result but we consider that this in itself may be discriminatory in a person who does not want, or wants to defer, a test. Since one of the fundamental aspects of consent is that it must be given freely and without coercion, one could question whether consent had been provided for such testing at all.
The request which the professional then made was for the wrong genetic test. It is worth noting that the laboratory did not question the request since few clinical details were provided on the request card, which, in turn, is not unusual. The negative result for HSMN was meaningless since it was the wrong test. Gary remains at 50% risk of having inherited an hMSH2 mutation, which puts him at high lifetime risk of developing colorectal cancer. However, he was falsely reassured that he had not inherited the familial tendency to cancer, and that surveillance was therefore not necessary.
While there has always been the potential for medical mistakes or errors to occur, the increasing complexity of modern medicine means that it has become harder for health-care professionals to deliver care safely and that there needs to be the acceptance that one cannot ‘know it all’ and that collaboration with other health-care professionals is essential. 6 Case reports regarding medical errors such as prescription of the wrong medication or of planned (or executed) surgery of the wrong anatomical region (for example, amputation of the wrong limb, or removing a healthy kidney) have been well documented. 7,8 We are not aware of any literature describing similar situations to the one in this report and that may reflect the limited provenance of genetic testing to date. While on the one hand, it is tempting to view a genetic test much like any other blood test, for example, a haemoglobin or cholesterol check, such tests are likely to be repeated over time. A genetic test – especially in the context of a known familial mutation – is definitive and indicates a germ-line inheritance that cannot be altered. Misunderstandings and misinterpretations of results are therefore more likely to have serious consequences, especially if medical management is altered, or not initiated, as a result of such tests. Successful ‘mainstreaming’ of genetics will therefore need to consider how such errors can best be minimized.
Once this error had come to light, a multidisciplinary team meeting discussed how to manage the situation. In accordance with Levinson et al., 9 who suggest that ethical and practical obligations compel a health professional to disclose harmful errors to patients, Gary was told in a genetic clinic appointment that the wrong test had been performed and that he had in fact not been tested for the bowel cancer gene. To date Gary remains untested with a 50% chance of having inherited the MSH2 gene mutation. Discovery and disclosure of the error was of value to Gary because he was now offered two-yearly colonoscopy surveillance and he knows that at some point he would like to have the genetic test. He also knows that he may have passed the gene mutation on to his offspring, who are currently all under 18.
This case highlights the importance of good communication and collaboration between genetic and mainstream specialties as well as the need for mainstream specialties to engage with ongoing genetics education. While mainstream specialists are likely to have other medical priorities, they will need to develop an awareness of the extent and limits of their genetic knowledge and be able to liaise with genetics services where appropriate. The importance of educating health-care professionals to enable them to understand and utilize basic genetic principles, including probability and risk assessment, and to communicate these effectively has been widely advocated and the potential clinical risks of not doing so illustrated. 10 However, this case illustrates that there is still scope for improvement. Not only was Gary wrongly informed about his own risks and declined appropriate surveillance, but the potential (future) risks to his children were therefore also not recognized.
Although we do not wish to suggest that genetic tests are fundamentally different from other blood tests – we do not subscribe to a genetic exceptionalist approach – we do consider that the implications of genetic testing can be particularly complex. The genetic mechanisms, the risks and uncertainties associated with a test, yet the irreversibility of any test result, the implications of results for other family members and the possible perceptions of stigmatization or guilt, mean that careful discussions and facilitation of decisions are required before testing is ordered.
The successful ‘mainstreaming’ of genetics and genomics will require health-care professionals to be clear about their individual roles, boundaries and limitations regarding the provision of genetic information, genetic testing, risk assessment and management. New ways of working and integration need to be considered alongside developments in the laboratory. In the UK, the development of the National Genetics Education and Development Centre and their provision of genetic competencies for non-genetic specialties are beginning to address the issue of genetics education. 11 However, communication and collaboration between genetics services, other secondary care services and primary care will be necessary at both local and national levels.