Genetic testing for Huntington Disease
How to recognize Huntington's disease: Q&A on the Genetic Test
The mutation that causes Huntington's disease consists in the increase in the number of three DNA molecules: Cytosine, Adenine, Guanine (CAG) in the HTT gene, located on the short arm of chromosome 4. When these three letters are repeated more than 36 times, there is the genetic mutation. The only way to know for sure if you are a mutation carrier is to undergo a genetic test which, however, cannot be considered a mere 'laboratory procedure', because the outcome opens a window on our future. We therefore need to understand in advance if and to what extent we are ready to open that window. The decision to undergo the test is personal. No one should be forsed by a third party. International guidelines recommend accompanying people towards an informed decision, with a path of genetic and psychological counseling.
What is the genetic test for HD?
The genetic test is 1) a procedure that requires a blood sample, 2) a laboratory methodology and 3) a personalized counseling path
How is the genetic test requested?
If there are symptoms, the test is requested by the doctor to confirm the clinical diagnosis (confirmation genetic test);
If you are at-risk, even without signs of disease, and you want to know in advance if the mutation has been inherited, you can ask your doctor for the test (predictive genetic test);
In case of pregnancy, it is possible to carry out a test on the fetus through chorionic villus sampling within the twelfth week (prenatal genetic test)
How is genetic testing technically performed?
Through a blood sample, DNA extraction from blood lymphocytes and an amplification technique of the DNA tract that hosts the mutation responsible for the disease with a method called Polymerase Chain Reaction (PCR).
Is the blood collected on the first visit?
No, the sample is taken during the counseling process, after the person at risk of the disease has had time to reflect. Usually at least a week after the first meeting.
How long does it take to deliver the report?
Usually one month after the withdrawal. Currently, due to Covid, the average time is about 2 months
How much does the genetic test cost?
If you have a family history of Huntington's disease, you are entitled to a referral with transitional code R99 (suspected rare disease) and the test is free of charge.
Is it possible to test children?
No, unless there is a clinical suspicion. (Anderson et al., Clin. Genet 2014)
What information does the genetic test give?
If the test is positive (mutation equal to or greater than 36 CAG): the disease may express itself earlier than when the parent became ill. We cannot know exactly when this will happen. In general, for the length of the mutation included between 36 and 39, it is possible to have an onset very late in life.
If the test is negative: you have not inherited the mutation and will not pass it on to our children.
If the test shows a so-called intermediate length (27-35 CAG) there is a risk, very low, that male parents may transmit the disease.
How is the result of the genetic test interpreted?
The genetic mutation is present if the number of repeated CAGs is equal to or greater than 36.
10-26 CAG: negative test (no disease, no risk for children)
27-35 CAG: intermediate result (no disease, with exceptions; theoretical risk for children <50% exceptional condition, very rare cases of new mutations)
36-39 CAG: low penetrance: yes illness, with exceptions; yes risk for children (50%)
equal to or > than 40 CAG: complete penetrance (yes illness, risk for children 50%)
equal to or > than 60 CAG: it is possible that the disease has a pediatric onset (Fusilli et al., Lancet Neurol 2018)
Can the number of CAGs change over the years?
The number of CAGs does not change in the blood cells or in any case we are not able to detect changes after years. It is possible that the length of the mutated tract may vary in some areas of the brain and tends to change over time. This thing is still under study.
If I look at my parent's test result, can I predict how many triplets I have possibly inherited?
No, but children tend to have a greater expansion and to anticipate the age of onset with respect to the affected parent
How long does the counselling last?
Usually at least three interviews are carried out over a couple of months. In any case, the time and number of interviews depends on the different situations
What is the difference between counseling and psychotherapy?
Counseling deals with non-specific problems, not related to psychopathological problems (such as anxiety and depression). Through counseling we provide the information necessary to be able to make a decision in a difficult and / or doubtful situation. Psychotherapy, on the other hand, deals with the complex relationship between emotions, thoughts and behaviors, highlighting how psychological problems are often the product of a dysfunctional relationship between these three aspects.
If the psychologist thinks I'm not ready, can he stop me from taking the test?
Absolutely not. The counseling process is not intended to 'bar' the way towards the decision to know one's genetic situation.
If I am tested positive, can I donate my blood?
We are currently unable to comment on this, as scientific research is still studying this aspect.
However, we see no contraindications to the current state of knowledge.
