20 World Health • 49th Year, No. 5, September-october 1996

Ethical aspects of early diagnosis of genetic diseases Kine Berg

Members of families at risk of certain genetic diseases should be offered treatment and advice on prevention.

Genetic diseases include dis­eases caused by a mutant gene

. at a single locus (Mendelian diseases), disorders caused by nu­merical or structural chromosomal anomalies, and diseases or malfor­mations caused by the action of several genes or by interaction be­tween genes and environmental factors . Although most single-gene diseases and chromosomal disorders are rare the aggregate health burden they impose is formidable. The most frequent of the single-gene disorders is autosomal dominant hypercholes­terolaemia, which in some popula­tions occurs with a frequency varying from 1 in 300 to 1 in 500.

More frequent is the case in which several genes as well as envi­ronmental factors contribute to the development of disease. The genetic contribution to this etiology is to create a predisposition to develop such ailments as cardiovascular diseases (in particular when they occur at a relatively young age), certain cancers (such as breast cancer occurring at a relatively young age, or colon cancer), asthma and psy­choses. Some of these diseases are among the major causes of death in developed countries.

Early detection of genetic predisposition requires a family approach.

Approaches to genetic diseases For several of the rare genetic disor­ders there is no efficient therapy available, so preventive measures are particularly important. Genetic counselling and prenatal diagnosis are instruments in the attempts to combat genetic diseases, and popula­tion screening may be another instru­ment in cases where early treatment is possible. The science of medical genetics also plays an important role in providing precise diagnosis, in­creasing our understanding of the molecular basis of diseases, and identifying disease-susceptible states.

One characteristic of genetic disorders is that knowledge derived from one patient may be of impor­tance for other family members. The genetic approach to such diseases is a family approach rather than one exclusively focused on individuals, and an important prerequisite is the availability of data on previously examined members of the family.

Early diagnosis makes prevention and treatment possible

Early detection of genetic predisposi­tion makes it possible to take effi­cient preventive measures when these are available, such as reduction of blood lipids and changes of lifestyle when there is a risk of coro­nary heart disease, or preventive removal of the colon in intestinal polyposis with cancer risk. Early diagnosis and treatment are also made possible, for example by fre­quent breast examinations in persons with genetic risk of breast cancer. Presymptomatic diagnosis of a dis­ease such as Huntington's chorea (a chronic progressive disorder charac­terized by involuntary jerky move­ments and mental deterioration) provides information of importance for reproductive choices or other planning for life in persons at risk who specifically ask to be examined. It is a prerequisite for both categories

World Health • 49th Year, No.5, September-October 1996

of examination that they are only offered on a voluntary and fully informed basis, and that test results are completely confidential.

Ethical aspects of early diagnosis It is well accepted that early diagno­sis should be made of disorders such as phenylketonuria and haemophilia, where early treatment would totally change the outlook for the child -dietary for the former, and treatment of bleeding for the latter.

At face value, it would seem uncontroversial to offer early detec­tion of disorders manifesting them­selves in adulthood, where life-saving treatment or preventive measures are available. However, autosomal dominant hypercholes­terolaemia and genetic predisposition to heart disease have provoked unex­pected reactions in some societies. In Norway, both the media and the data protection authorities have argued against an active offer of examination, efficient lipid-lowering treatment and lifestyle advice to persons known to be at risk for a given disorder because a parent or other close relative has it.

One argument is that "one should not turn healthy people into patients", and the point that informa­tion about genetic disease risk can cause anxiety has merit. Accordingly, physicians or other health workers should limit them­selves to making it clear that the at­risk person could derive significant advantage from being examined for a possible disease risk, because there are treatment or prevention opportu­nities available, should the risk status be confirmed. Only if the person chooses to receive information or to be examined should the physician proceed.

The argument that it is the physi­cian's duty not to divulge any infor­mation about other members of a family also has merits , but it is possi­ble to provide information about risks without providing it about specific persons. After all, a physi­cian 's duty to be silent has the sole

A sickle-cell clinic in jamaica. The control and treatment of genetic disorders entail a whole new order of ethical issues.

purpose of protecting people, and to "protect" a person from receiving life-extending, lipid-lowering treat­ment for hypercholesterolaemia was never the intention of laws governing the confidentiality of medical infor­mation. Using this argument to oppose the prevention or treatment of serious disease appears to be unethi­cal.

As regards familial hypercholes­terolaemia, for instance, the evidence is that a majority of people would want to be informed if they might be carriers of that gene. A majority also believe that the physician has a duty to inform individuals at risk. Instead of struggling with the question of how valid a presumed "right not to know" might be, efforts should now be made to ensure that at-risk per­sons in families are offered treatment and advice on prevention in a con­structive way that creates as little anxiety as possible. An international "code of conduct" would be useful.

Is there a valid ''right not to know"? Respect for people's autonomous decisions makes it necessary to accept that some people choose not to know in matters concerning their own health and prognosis. However, this choice is ethically defensible only if it has no consequences for other people. If severe disease or early death seem likely, there must be an ethical obligation to know this and

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to communicate it to a spouse or spouse-to-be, since the spouse's future life may be very much influ­enced by the fate of the at-risk per­son. Choosing not to know or not to communicate would be to remove the spouse's right to make choices for the future, for example on having children.

Sharing genes, fate and knowledge If a person learns that he or she has classical familial hypercholestero­laemia, brothers and sisters will be at very high risk of also having this dangerous disease- which today can be treated with effective lipid-lower­ing drugs. Although the person might choose not to take drugs and not to make any changes in lifestyle despite knowing that he or she has a dangerous disease, it may not be ethically defensible to abstain from informing brothers and sisters about the potential risk. Not informing them would mean taking away the possibility of making a choice that had been available to the person in whom the condition was originally diagnosed. The correct ethical action would be to make sure that brothers and sisters have the same opportunity to choose as oneself.

Where a genetic predisposition exists in a family, the principle of autonomous decision can no longer be absolute but must yield to the new principle that people sharing a given fate because they share certain genes should act in solidarity. One conse­quence would be to share the vital information, and another would be to participate in research that could make life better for the group in future . The principle that a physi­cian may not offer unsolicited treat­ment or advice to at-risk persons should be modified where failure to act on the part of the physician could cause harm or death. In such cases, a duty to offer information should be given consideration. •

Professor Kare Berg is Professor of Medicine and Chairman of Medical Genetics at the University of Oslo, P. 0. Box I 036, Blindern, N-()3 15 Oslo, Norway.