Multiple endocrine neoplasia type 2 (MEN-2) may be the ideal disease
for presymptomatic genetic testing. The syndrome has an autosomal
dominant pattern of inheritance and includes medullary thyroid
carcinoma, pheochromocytomas, and, sometimes, parathyroid adenomas.
The risk of medullary thyroid carcinoma in affected persons is
The Netherlands group previously found that all persons diagnosed
by genetic testing harbored small foci of medullary thyroid carcinoma,
whether or not their plasma calcitonin level was abnormal. Furthermore,
the cancer was curable in each case. This represents a significant
advance over periodic biochemical testing, which does not detect
some thyroid cancers early enough for cure. Also, half of those
who undergo periodic testing are not carriers of the mutant gene
Multiple endocrine neoplasia type 2 is caused by missense mutations
in the RET proto-oncogene. Carriers of the mutant gene can be
identified by genetic testing once the specific disease-causing
mutation for an affected family has been identified. Non-gene
carriers can then be spared further testing and concern for themselves
and their offspring. Gene carriers can undergo curative thyroid
surgery and appropriate observation and screening for other possible
tumors; these individuals also will know that testing is necessary
for their offspring.
The present study addresses the psychological and social consequences
of genetic testing for MEN-2. The investigators were careful to
follow the accepted ethical approach to testing, which includes
education and counseling before testing, at the time results are
given, and after disclosure. The most notable results of the study
included feelings of anxiety and depression, mixed with relief,
in subjects who tested positive, and relief coupled with worry
in those who tested negative. Most important, subjects usually
received appropriate support from family members, and any early
negative psychologic impact had resolved by 1 year after testing.
Adverse social impact, such as insurance discrimination, was not
apparent, but could not really be judged without longer follow-up.
How Does Genetic Testing Differ From Presymptomatic Disease
This study is a careful, meaningful examination of the psychological
and social risk issues associated with genetic testing. But what
is all the fuss about these issues anyway? For years physicians
have been involved in the diagnosis of presymptomatic disease.
Measurement of blood pressure is a good example. High blood pressure
usually is not considered a disease by itself, but it predicts
the development of cardiovascular and cerebrovascular problems.
Cholesterol measurements are similar in this regard. There certainly
are psychological and social consequences of having high blood
pressure or high cholesterol, and their presence always affects
insurance. But we never give counseling or obtain informed consent
about the possible consequences of measuring blood pressure or
cholesterol. If, however, a genetic test became available that
identified those who would develop essential hypertension (a likely
event), then counseling and informed consent for testing would
become ethically necessary. What's the difference?
Several factors have focused critical attention on the psychological
and social impact of genetic testing. First, an aura and mystique
surround any new technology. These result in increased critical
Second, there has been a heightened concern about ethics and informed
consent in general. Some of this concern derives from an improved
ability to quantitate such issues, as the present study illustrates.
However, there is also a genuine increased awareness of these
matters. It is unlikely that today's health-care workers are more
ethical or patient-oriented than their predecessors. Rather, the
patient-physician relationship has evolved from a relationship
based on authority to one based on education and interaction.
Third, there are, indeed, some very real differences between genetic
testing and traditional disease assessment. Genetic testing is
extremely precise; who does and does not have a predisposition
is determined with near certainty. Genetic testing is also very
personal; it derives from the very stuff, DNA, that determines
who and what we are. We can't change our genes like we can treat
blood pressure or cholesterol.
Most important, genetic testing is almost always applied presymptomatically,
while most traditional medical testing is done to evaluate symptoms.
It is assumed that a diagnosis is important once symptoms develop.
But how crucial is it to reach a diagnosis before symptoms of
a disease occur? It may be important for some conditions but unimportant
and even harmful for others. Genetic testing, by itself, ignores
how important or unimportant, and how beneficial or harmful, knowledge
of a presymptomatic diagnosis may be.
The genetic causes of disease are being studied because the requisite
technology is now available and because genetic treatment may
eventually become possible. As the field has progressed, however,
genetic diagnosis has become a reality for many diseases, but
genetic treatment, so far, has become possible for almost none.
Available treatments or the lack thereof remain unchanged.
Traditional medical approaches have usually developed for conditions
in which a difference can be made. Population screening is done
for cervical cancer, for example, because it can be cured, but
not for lung cancer, because it cannot. Blood pressure and cholesterol
are routinely measured because they can be treated and their consequences
minimized. Genetic testing again ignores whether anything clinically
useful can come of the test.
Making the Decision
For the above reasons, the decision to use genetic testing must
weigh the existing medical benefits of testing against the psychological
and social risks (or benefits). It is most important to recognize
that these risks and benefits differ markedly for each disease
or disease predisposition under consideration. At one extreme,
if successful prevention and treatment are already available for
the disease in question, and only earlier diagnosis is needed,
then genetic testing is a welcome addition. The medical benefit
of testing in such a situation is so great that the psychological
and social issues are of minimal consequence and may well take
care of themselves. The article by Grosfeld et al represents a
situation close to this extreme.
At the other extreme are severe diseases for which there currently
is no prevention or treatment. In such instances, genetic diagnosis
serves only to relieve worry in the unaffected person, but at
the probable expense of those who are found to be affected. Social
and psychological concerns in this situation become paramount.
They are the determining factors in the decision of whether or
not to undergo the genetic test. Huntington's disease is the obvious
example of this situation.
Most diseases fall between these two extremes.
Problems of Genetic Testing Compounded in Children
The problems of genetic testing are further compounded in children.
Parents almost always want their children to be tested, but what
they really want to know is that their children are unaffected.
Children's rights must sometimes be invoked to avoid potentially
dire social consequences. Parents' intentions cannot be questioned,
but their understanding of the consequences of testing is often
incomplete. The testing of children was of little question in
the present study in which the parents clearly understood the
medical benefit of such testing.
In summary, the medical benefits of genetic testing must be weighed
against the psychological and social consequences for each disease
individually. The authors carefully identify the social and psychological
issues that need to be considered. The degree of benefit or harm
will differ for each disease, as will the medical consequences.
Patients, physicians, and genetic counselors must all be aware
of these issues. Patients ultimately decide whether or not to
undergo genetic testing, but that decision is influenced greatly
by how the issues are presented. Significant responsibility, therefore,
rests with health-care workers to be aware of the positive and
negative consequences of testing and how to explain them. Patients
almost always have an inherent interest in knowing whether they
have a disease predisposition, but they must be able to answer
the question, "Is it in my best interest to know?"