A woman stares pensively out her bedroom window. Today is her twenty-seventh
birthday. Most people have the whole rest of their lives to look forward to when staring out the window at this age, but not
Sylvia. She isn't sure. Ten years ago her mother was diagnosed with Huntington's Disease, a late-onset genetic disorder, and
Sylvia was forced to watch her mother deteriorate to the point where she could no longer take care of herself.
Sylvia and her brother had to put their mother in a home. Now Sylvia faces a lot
of decisions and dilemmas. She has recently married. Now, she and her husband are trying to decide whether or not to have
children, and the local hospital just hired her as a physician's assistant.
But how long does she have until she begins to deteriorate like her mother? Or maybe
she is the lucky one; maybe she didn't inherit this gene from her mother. There are many uncertainties in her future right
now. There is one way to erase these uncertainties, and that is predictive testing for Huntington's disease. But is this the
right choice for her?
Huntington's Disease is an autosomal dominant degenerative disorder of the central nervous system. This
means that if either parent has the disease there is at least a fifty percent chance that the offspring will develop the disease.
There is complete penetrance, so all who have the disease will develop symptoms. It is a late-onset genetic disorder in which
symptoms begin to appear in the late thirties or early forties. There are some cases however of juvenile or geriatric Huntington's
Disease. There is currently no cure, so to those who develop the disease, it is lethal.
The most characteristic feature, and the symptom which is used to first diagnosis Huntington's, is chorea.
Chorea can be characterized by a series of tics affecting the face and limbs. In more advanced Huntington's the chorea turns
into athetosis or dystonia in which the affected person experiences a "writhing quality" (Furtado 7).
There are other characteristics of this deadly disease too in which the patient slowly loses control
of all involuntary movements. Eye movement abnormalities are sometimes excessive blinking or gazing.
There are psychological and sexual changes as well as cognitive dysfunction and a decline of memory.
Patients usually become irritable, impulsive, and highly suspicious of others. They also experience depression, become anti-social,
and develop delusional thinking. There is a high suicide rate among those with Huntington's, but there is a discrepancy about
whether it is because of the depression, or because the disease is emotionally painful and lethal without any hope of recovery.
As far as sexual activity is concerned, people either become hyper-sexual, hypo-sexual, or take part in exhibitionism.
Reduction in number of words produced, difficulty in comprehension and articulation as well as visuospatial
problems are some of the cognitive dysfunctions.
Recognition memory in patients with this disease is usually normal, but remote memory in which people
try to recall the past, or even the present, is what is affected by the disease (Furtado 8).
Huntington's is an awful disease that takes control of the brain and causes slow atrophy until death,
but luckily it is a rare disease. Only one in ten thousand people are affected. One hundred and fifty thousand relatives of
Huntington's patients are at risk, but the only way to tell whether they have inherited the mutant gene or not is by the duration
of time or by predictive testing (Saltus 1).
So what is predictive testing?
Predictive testing is a type of genetic testing for late-onset disorders. These types of tests give
information on the genetic makeup of the individual and let him or her know if they have the mutant gene responsible for causing
the disease.
These tests "predict" the future of the patient. Individuals who wish to be tested may if there is a
history of the disease in the family, the person is already showing symptoms of the disorder, or if the person is afraid of
passing the gene onto his or her children.
The Human Genome Project is a project designed to map all one hundred thousand genes in the human genome
and know their function. Geneticists say it will be completed by the year 2005. Because of this project geneticists are able
to do predictive testing (Cook-Deegan 20). Linkage testing, or indirect testing, is used when the specific location of the
gene is unknown, but it can be located within a certain region of a chromosome. This kind of testing however requires additional
DNA from affected family members.
Recently people have been able to use direct testing to examine genes or markers placed near the genes
for inspection of the mutation. There are always the possibilities of false negatives or false positives when dealing with
genetic testing, but these do not happen very frequently because testing is done numerous times, and the lab technicians are
highly trained to read the results carefully (ELSI 1).
Doctors have used both of the above techniques to test for Huntington's Disease. The goal was to isolate
the gene for the disease. The technique for doing this is called genetic linkage mapping. One defines segments of DNA with
chemical markers and then searches between them (Cook-Deegan 18). In 1983, J.F. Gusella and his coworkers found a Restriction
Fragment Length Polymorphism (RFLP) marker for the Huntington gene on chromosome four. This led to DNA linkage analyses.
These analyses were not always technically applicable because DNA from other affected family members
was needed in order to enable geneticists to search for these markers in people, some positive and some negative for Huntington's
Disease (Decruyenaere 3). But ten years later in 1993 the Huntington's gene was finally isolated. It was discovered that the
cause of the mutation in this specific gene was an expanded number of CAG triplet repeats at the beginning portion of the
gene.
Most people have eleven to thirty one repeats, but those with Huntington's Disease have more than thirty
eight of these triplets. Those whose number of triplets fall between these two ranges are known as "sporadic cases" because
doctor's can't be sure whether they have the defective gene or not.
Those with juvenile onset tend to have more triplets than those who get the disease later in life. This
time of onset is also related to the sex of the parent from whom the gene was passed. Those who do get juvenile Huntington's
usually inherit the gene from their fathers, and those who develop symptoms later in life usually inherit the gene from their
mothers.
The RNA carrying the mutated Huntington gene is found in all organs of the body, but is most commonly
found in the brain, and it is eventually translated into the protein huntingtin (Furtado 9). This explains why there is neuronal
degeneration in the basal ganglia and cerebral cortex which results in death fifteen to twenty years later (Decruyenaere 2).
Doctor's treat chorea by prescribing neuroleptics, such as haloperidol* or
tetrabenazine, which help suppress these abnormal movements. They are also able to treat the psychiatric problems, but there
is currently no treatment aside from symptomatic relief because there is currently no cure for Huntington's Disease (Furtado
10).
Although there is no cure for this disorder, presymptomatic testing is still available for those who
want it. Pre- and post-test counseling sessions are required though if the patient decides he or she wants to go through with
the testing.
Counseling is provided before and after the testing for the patient to make sure this is what he wants
to do and have the ability to deal with the emotional burden that accompanies genetic testing. What is the approach that most
genetic centers take when dealing with these tests?
There is a center for Human Genetics in Leuvan, Belgium which takes on a multi-disciplinary approach
to testing. A genetic counselor, a social worker or nurse, a psychologist, a psychiatrist, and a neurologist are the people
involved (Decruyenaere 5). There is a certain guideline which they follow when administering these tests. In the initial intake
session the patient goes over his or her family history. Expectations of the test, assessment of the genetic risk of the patient,
and information about the test, as well as the basic protocol of the test are also discussed in this stage.
The next stage is the psychological evaluation and decision counseling. Here the patient talks about
the burden Huntington's Disease has been to their family, and the role of genetic risk in the testee's life. The patient will
explore his or her motivations for taking the test, the potential impact of the results, and the coping mechanisms and means
of support that the patient has available. Afterwards there is a neurological examination.
The third stage is a meeting with all members of this "predictive testing team". They evaluate all the
data on their patient and note the final things which need to be discussed before administering the test.
Then there is the last pre-test counselling session in which all relevant items with regard to the test
are discussed. The individual makes a final decision to either withdraw from the testing, or postpone it, or to continue with
the testing in which case a blood sample is drawn and the DNA is analyzed.
The results are shared with the patient, and then there are a series of follow-up visits to keep track
of the emotional stability of the individual.
For those who test positive for the Huntington gene there are phone calls throughout the first week,
and then follow-up sessions after one week, one month, three months, one year, and are then continued on a yearly basis.
For those testing negative there are post-test counselling sessions after one month, one year, and finally
five years (Decruyenaere 6-7).
