Presymptomatic testing for Huntington's disease

Family history of Huntington's disease

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.

Genetic markers

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 relative's death.
• Adopted children may not know their genetic heritage, or early symptoms in an individual may be too slight to attract attention.

How is the presymptomatic test conducted?

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
• Follow-up

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 result.

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.

Blood screening

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 uterus.

Risks of testing

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.

How does a person decide whether to be tested?

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.

Emotional consequences

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 known.