Presymptomatic testing is used for people who have a family
history of Huntington's disease (HD) but have no symptoms
themselves. If either parent had HD, the person's chance would be
50-50. In the past, no laboratory test could positively identify
people carrying the HD gene--or those fated to develop HD--before
the onset of symptoms. That situation changed in 1983, when a team
of scientists located the first genetic marker for HD. That was the
initial step in developing a laboratory test for the disease.
A marker is a piece of DNA that lies near a gene and is usually
inherited with it. Discovery of the first HD marker allowed
scientists to locate the HD gene on chromosome 4. This led to the
development of a presymptomatic test for some individuals. However,
this test required blood or tissue samples from both affected and
unaffected family members in order to identify markers unique to
that particular family. For this reason, adopted individuals,
orphans, and people who had few living family members were unable
to use the test.
Discovery of the HD gene has led to a less expensive, simpler
and more accurate presymptomatic test. The new test uses CAG repeat
length to detect the presence of the HD mutation in blood.
Complications in presymptomatic testing
There are many complicating factors that reflect the complexity
of diagnosing HD. Examples include:
- No family history of HD can be found in a small number of
individuals with HD (1 to 3 percent).
- Some individuals may not be aware of their genetic legacy.
Sometimes a family member may conceal a genetic disorder from fear
of social stigma. A parent may not want to worry children, scare
them, or deter them from marrying.
- A family member may die of another cause before he or she
begins to show signs of HD. Sometimes, the cause of death for a
relative may not be known, or the family is not aware of a
- Adopted children may not know their genetic heritage, or early
symptoms in an individual may be too slight to attract
An individual who wishes to be tested should contact the nearest
testing center. (A list of such centers can be obtained from the
Huntington's Disease Society of America at 1-800-345-HDSA.) Most
testing should include the following components:
- A neurological examination
- Pretest counseling
Looking for clinical symptoms
The purpose of the neurological examination is to determine
whether or not the person requesting testing is showing any
clinical symptoms of HD. It is important to remember that if an
individual is showing even slight symptoms of HD, he or she risks
being diagnosed with the disease during the neurological
examination, even before the genetic test.
Weighing the benefits and risks
During pretest counseling, the individual will learn about HD,
about his or her own level of risk, and about the testing
procedure. The person will be told about the test's limitations,
the accuracy of the test, and possible outcomes. He or she can then
weigh the risks and benefits of testing and may even decide at that
time against pursuing further testing.
If a person decides to be tested, a team of highly trained
specialists will be involved, which may include neurologists,
genetic counselors, social workers, psychiatrists, and
psychologists. This team of professionals helps the at-risk person
decide if testing is the right thing to do and carefully prepares
the person for a negative, positive, or inconclusive test
Individuals who decide to continue the testing process should be
accompanied to counseling sessions by a spouse, a friend, or a
relative who is not at risk. Other interested family members may
participate in the counseling sessions if the individual being
tested so desires.
The genetic testing itself involves donating a small sample of
blood that is screened in the laboratory for the presence or
absence of the HD mutation. Testing may require a sample of DNA
from a closely related affected relative, preferably a parent, for
the purpose of confirming the diagnosis of HD in the family. This
is especially important if the family history for HD is unclear or
unusual in some way.
Results of the test should be given only in person and only to
the individual being tested. Test results are confidential.
Regardless of test results, follow-up is recommended.
Prenatal testing and testing children
In order to protect the interests of minors, including
confidentiality, testing is not recommended for those under the age
of 18 unless there is a compelling medical reason (for example, the
child is exhibiting symptoms).
Testing of a fetus (prenatal testing) presents special
challenges and risks. In fact, some centers do not perform genetic
testing on fetuses. Because a positive test result using direct
genetic testing means the at-risk parent is also a gene carrier,
at-risk individuals who are considering a pregnancy are advised to
seek genetic counseling prior to conception.
Some at-risk parents may wish to know the risk to their fetus
but not their own. In this situation, parents may opt for prenatal
testing using linked DNA markers rather than direct gene testing.
In this case, testing does not look for the HD gene itself but
instead indicates whether or not the fetus has inherited a
chromosome 4 from the affected grandparent or from the unaffected
grandparent on the side of the family with HD. If the test shows
that the fetus has inherited a chromosome 4 from the affected
grandparent, the parents then learn that the fetus's risk is the
same as the parent (50-50), but they learn nothing new about the
parent's risk. If the test shows that the fetus has inherited a
chromosome 4 from the unaffected grandparent, the risk to the fetus
is very low (less than 1%) in most cases.
Another option open to parents is in vitro fertilization with
pre-implantation screening. In this procedure, embryos are screened
to determine which ones carry the HD mutation. Embryos determined
not to have the HD gene mutation are then implanted in the woman's
There are emotional and practical consequences, not only for the
individual taking the test but for his or her entire family.Testing
is enormously complex and has been surrounded by considerable
controversy. For example, people with a positive test result may
risk losing health and life insurance, suffer loss of employment,
and other liabilities. People undergoing testing may wish to cover
the cost themselves, since coverage by an insurer may lead to loss
of health insurance in the event of a positive result, although
this may change in the future.
With the participation of health professionals and people from
families with HD, scientists have developed testing guidelines. All
individuals seeking a genetic test should obtain a copy of these
guidelines, either from their testing center or from the
organizations listed on the index page. These organizations have
information on sites that perform testing using the established
procedures.They strongly recommend that individuals avoid testing
that does not adhere to these guidelines.
The anxiety that comes from living with a 50 percent risk for HD
can be overwhelming. How does a young person make important choices
about long-term education, marriage, and children? How do older
parents of adult children cope with their fears about children and
grandchildren? How do people come to terms with the ambiguity and
uncertainty of living at risk?
Some individuals choose to undergo the test out of a desire for
greater certainty about their genetic status. They believe the test
will enable them to make more informed decisions about the future.
Others choose not to take the test. They are able to make peace
with the uncertainty of being at risk, preferring to forego the
emotional consequences of a positive result, as well as possible
losses of insurance and employment. There is no right or wrong
decision, as each choice is highly individual. The guidelines for
genetic testing for HD, discussed in the previous section, were
developed to help people with this life-changing choice.
Whatever the results of genetic testing, the at-risk individual
and family members can expect powerful and complex emotional
responses. The health and happiness of spouses, brothers and
sisters, children, parents, and grandparents are affected by a
positive test result, as are an individual's friends, work
associates, neighbors, and others. Because receiving test results
may prove to be devastating, testing guidelines call for continued
counseling even after the test is complete and the results are