Late onset genetic disease: where ignorance is bliss, is it folly to inform relatives?
BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7160.744 (Published 12 September 1998) Cite this as: BMJ 1998;317:744
- Jon Torgny R Wilcke (twilcke{at}rh.dk), senior registrar
One aspect of the rapid advances in molecular genetics is the capacity to identify genetic predispositions in a particular individual, where previously we made risk assessments based on aggregate or population observations. 1 2
Specific genetic data on one person unavoidably involve the family. They reveal information not only about the person examined but about their relatives and future children, who may be sick or carriers of the disease or trait. The proband, the family, and the genetic counsellor are faced with the problem of communicating news of the high risk for a genetic disease to healthy (asymptomatic) family members. They are also faced with making a moral choice between the right of family members to be privy to this information and their right to “blissful ignorance.”
Summary points
Knowledge of a genetic disease in an individual raises issues of whether and how this information should be communicated to his or her family
The strategy for approaching and informing at risk relatives should depend on the genetic disease—on whether an unfavourable outcome is avoidable or not
The initial approach to relatives should be made by the proband and be supported by information from a genetic counsellor
The proband and counsellor have an obligation to ensure that relatives are informed about the risk of severe, preventable genetic disease
Moral obligations and ethical questions
Most genetic counsellors believe that family members have a moral obligation to share genetic information with each other.3 Many counsellors also believe that an uninvited approach to relatives at risk for a genetic disease is ethically questionable, irrespective of the disease. The Danish Ethics Council recently stated that “no unsolicited approach may be made by the health authorities in the case of an examination that may show any hereditary disease in the family. This should also be the case in situations where it can have serious consequences.”4
This recommendation is not in line with the Danish α1 antitrypsin register's long tradition of contacting and informing directly the relatives of patients with α1 antitrypsin deficiency of their risk and options for prevention. I believe that the strategy for approaching and informing relatives who are at risk should depend on the genetic disease in question. The strategy and the argument must be different for disorders such as Huntington's disease—where there is no way of avoiding the outcome—and autosomal dominant polycystic kidney disease, hereditary hypercholesterolaemia, or α1 antitrypsin deficiency—where a small change in lifestyle or similar options can prevent disability and early death. Kielstein has expressed it thus: “As PKD [polycystic kidney disease] is one of the abnormalities where careful lifestyle management can prevent early and avoidable risks, some of them life threatening, there seems to be a ‘duty to know’ on the side of the patient, and an ‘obligation to inform’ on the side of the physician.” 5 6
Example: α1 antitrypsin deficiency
To illustrate my analysis I have chosen to look at a typical case of α1 antitrypsin deficiency. Nina consults her doctor because she is becoming increasingly short of breath. She is 35 years old and has smoked 20 cigarettes a day for the past 20 years. Nina's chest radiograph shows emphysema, her lung function is 35% of predicted, and a blood sample shows she has severe α1 antitrypsin deficiency—homozygous genotype piZZ. The doctor tells Nina that α1 antitrypsin deficiency is inherited as an autosomal recessive disease. The risk of her brother having it is 25%, and the risk for her children and his children is about 2% (1 in 1600 Scandinavians is homozygous genotype piZZ, and 4-5% are carriers of piMZ). 7 8 The doctor also tells Nina that the specific diagnosis of carriers and affected people is easy and valid,9 and that smoking is the decisive risk factor. The only certain way to avoid chronic pulmonary insufficiency is to refrain from smoking. Patients with α1 antitrypsin deficiency who stop smoking have a reduced annual decline in lung function and increased survival compared with those who continue to smoke.10 Symptoms start at around 30-40 years of age, and median age at death is 50 years for smokers, while survival in never smokers is the same as that in the normal population. 11 12
The right to know
Our experience with people in the position of Nina or her brother is that they wish to communicate and to be given information. Although many genetic counsellors make an effort to disseminate genetic information within affected families, they may not make a direct and unsolicited approach to relatives because they do not know what the relatives' attitudes are and whether the relatives want to know about their increased risks.
The Danish Ethics Council states that communicating genetic information within a family is solely a family matter, and the initiative must come from the proband. This view is based primarily on a consequentialist principle that focuses on possible harm to the relatives. “This [an unsolicited approach] can create undue anxiety on the part of relatives concerned and, at worst, encroach radically on their lives, through no wish of their own.”4
Weighing up consequences
Knowing about a fate (genetic predisposition) whose likelihood and time schedule is uncertain and which requires you to make life, family, and employment/career plans and to tackle problems of reduced employability and insurability has considerable consequences. Certainly, knowing about α1 antitrypsin deficiency forces Nina's brother to consider difficult problems and make hard decisions, but it also has positive aspects. Not to inform him might have serious consequences too, because he might expose himself to smoking, a risk that could be avoided. If Nina's brother is more than 25 years old and does not smoke, it is unlikely that he will start. Information about the risks of α1 antitrypsin deficiency may be of limited use, except to reassure him that he has little to fear since those who have never smoked rarely develop severe disease. Nevertheless, the consequences of an active approach and information policy for someone in the position of Nina's brother are preferable to the consequences of remaining in ignorance.
Knowledge is power
Regardless of the consequences for Nina's brother, information puts him in a position to make his own decisions about smoking, to attempt to prevent his children and relatives from smoking, and to take precautions when choosing an occupation. People who know that they have an appreciably increased risk of disease from smoking are more likely to stop. This was seen when 67% of Danes registered as having α1 antitrypsin deficiency, genotype piZZ, quit smoking.12
Doctor knows best…
If, as recommended by the Danish Ethics Council, we decide not to inform Nina's brother, to prevent him becoming anxious, we are doing this for his own good. However, the ethics council's reasoning would prevent the health authority from approaching Nina's brother under any circumstances, and from ensuring that he is given the information needed to make his own decisions and choices. The essence of this policy is that the amount of information given to someone in Nina's brother's situation should be based on what the ethicist or doctor think is best for that person. Many people at risk for α1 antitrypsin deficiency would be within their rights to question why they had not been told (if this were the case) and given the opportunity to take preventive measures and stop smoking. This question puts the concept of paternalism and the moral principle of respect for the patient's autonomy at the centre of the debate on the patient-doctor relationship and on unsolicited approaches by counsellors to relatives of probands.
Autonomy and paternalism
The moral principle of respect for autonomy means respecting someone's capacity to reflect on preferences and desires and the decisions they make concerning their own life.17 An autonomous person should be free to decide to take great risks (for example, to smoke), however foolish these may be. But he or she should know what assumptions are being made, and should have enough knowledge on which to base decisions. People who expose themselves unwittingly to risk have not, in any considered way, chosen to take that risk. Smoking is dangerous for most people, but it is lethal for someone with α1 antitrypsin deficiency. Therefore, to respect his right to autonomy, the genetic counsellor or Nina must approach Nina's brother and give him the information he needs to make informed decisions. Not ensuring that Nina's brother is told of his increased risk of pulmonary insufficiency shows a complete lack of respect for him as an autonomous person.
Paternalism is the substitution of one person's judgment for that of another in what the first considers to be the other's best interest. If the other person is an autonomous agent, a paternalistic act is also a denial of their autonomy. When the Danish Ethics Council recommends, or a doctor decides, to deny Nina's brother the knowledge needed to make autonomous decisions because they think he should not be made anxious, they are behaving in a paternalistic way. In the case of α1 antitrypsin deficiency, this form of paternalism would be very hard to justify, since it would not have the best consequences for Nina's brother. In α1 antitrypsin deficiency there is no conflict between respect for autonomy and consequentialist reasons for not informing relatives, whereas the opposite may hold for Huntington's disease.
The right not to know
The situation is different if someone has knowingly and freely stated that they prefer to leave difficult problems aside and do not want to be informed or approached by a doctor about an increased risk for this or any disease. In this case, it would be a violation of autonomy to insist on informing that person, and an act of paternalism (perhaps justified on occasions) if this were based on a judgment about what constitutes that person's best interests. With regard to Nina's brother, therefore, respect would also have to be shown for any wish he had expressed to remain in ignorance. Usually, there is no way of knowing a person's wishes … and if that person is and remains totally ignorant, they have no opportunity to consider the problem. If Nina's brother is to be told about the risk of α1 antitrypsin deficiency, we have to approach and inform him one way or another, without his informed consent to such an approach. Should we leave him alone or are we in a situation in which exception to the rule of informed consent is reasonable?
Reasonable judgment
What would be a reasonable judgment about what a person in the situation of Nina's brother would prefer? An unsolicited approach to Nina's brother gives him the possibility of being provided with the information necessary to make autonomous decisions. In the case of α1 antitrypsin deficiency, it is reasonable to believe that the benefits1of knowing outweigh the consequences of knowing. There is little reason to suppose that someone in Nina's brother's situation would prefer to remain in ignorance. Perhaps some people might prefer to live in a “fool's paradise,” but without positive evidence of this disposition it is more reasonable to assume the opposite.
The importance of privacy
The right to privacy concerns the right to exclude others, a right not to be scrutinised by others, and the right to control information about yourself that is available to others.13 What is at issue with the right to privacy is people's right to control information about themselves that comes from themselves. This contrasts with respect for autonomy, where the concern is for people's right to control information about themselves that comes to them.14 In the context of an unsolicited approach from a genetic counsellor, privacy often centres on issues such as where the counsellor obtained personal information. This is reflected in the questions that are often asked, such as, “Where did you get my name and address from?”
An unsolicited approach from a counsellor to Nina's brother constitutes information about him coming to him. The classic understanding of privacy is not violated by the approach itself and by handing over some possibly harmful—or at least not very pleasant—information to him. On the other hand, the right to privacy means that Nina's brother has the right to determine in what ways and for what purposes personal information about him is to be used. If the genetic counsellor asks Nina about her relatives and Nina discloses her brother's identity, his right to privacy has been violated. The counsellor now knows that Nina's brother is at increased risk for α1 antitrypsin deficiency. A widely (perhaps) known family relationship—being Nina's brother—is transformed into sensitive information when genetic data are added.
To reduce relatives' feeling of having their privacy violated, counsellors at the Danish register never make inquiries about relatives through any public register, but always through a written request to the proband. Probands are asked to inform their relatives of an approach, in advance if possible, so that everyone involved has an opportunity to stop this, and it is emphasised that no one is obliged to give any information to the register.
Who should approach relatives?
Some probands may prefer to inform at risk relatives themselves, while others prefer a health professional to contact relatives directly. Furthermore, some probands cannot or do not want to inform relatives themselves because of physical limitations or difficult relationships with family members.
In considering this issue the unofficial national council of bioethics in the United Kingdom,14 the Nuffield Council of Ethics, has stated that “the primary responsibility for communicating genetic information to a family member or third party lies with the individual and not with the doctor, who however may do this on request of the person concerned.”15 In the case of preventable diseases such as lung insufficiency due to α1 antitrypsin deficiency, I believe that both the proband and the genetic counsellor have an obligation to ensure that relatives are informed. The preferred way of informing relatives is by an initial approach from the proband supported by counselling and written information from the genetic counsellor.
Both the approach by the genetic counsellor and the proband have positive and negative aspects. I believe that direct genetic counselling of those involved is the best way of providing reliable information independently of personal/family preferences, and ensures that most people at risk are able to exercise their right to autonomous decisions. However, experience from the United States is frightening: entirely asymptomatic people labelled (possibly erroneously) as having a genetic predisposition are faced with discrimination, such as inability to get a job, health insurance, or life insurance; inability to change jobs or move to another state because of the risk of losing insurance; and not being allowed to adopt children.16 Such social discrimination can be avoided if the proband is able to keep the genetic knowledge within the family.
In conclusion
My conclusion is that Nina's brother should be informed. Both Nina and the genetic counsellor should ensure that he is approached and told about his increased risk of pulmonary insufficiency due to α1 antitrypsin deficiency and smoking, unless they have good evidence to suggest that he would not want to be told. The initial approach to relatives should preferably be made by the affected family member, and should be supported by written information through a personal mailed letter from the register or, less officially, through the proband; personal genetic counselling of all family members who might want it; and easy and free access to testing.
In theory, it seems fair to change and limit the Danish register's approach to those relatives who would benefit from a change in lifestyle, such as avoiding smoking. However, non-smokers too may have an interest in being informed so that they can prevent their children, if any, from smoking. The results of a continuing interview and questionnaire study of affected families and a randomly selected control population are awaited before any changes in policy are made.
Acknowledgments
Funding: None.
Conflict of interest: None.