Most people at risk for Huntington’s decide not to undergo genetic testing for the disease due to the lack of effective treatment — and because they can’t unlearn the knowledge that they may have the neurodegenerative disorder, a study shows.
Researchers say choosing not to know if one is a carrier of the Huntington’s gene is a decision that deserves the respect and understanding of doctors and genetic counselors, who nevertheless should offer them supportive counseling.
The study,”The choice not to undergo genetic testing for Huntington disease: Results from the PHAROS study,” was published in the journal Clinical Genetics.
“Back in 1993, when the genetic mutation causing HD [Huntington’s disease] was discovered, we anticipated that many people at risk would want to be tested, just to deal with the uncertainty, but that is not the case. Only about 10 to 15 percent of people who know they are at risk for HD have been tested since the test became available, and that percentage really hasn’t changed much over time. This study shows there are important, relevant reasons why people don’t want to be tested,” Karen E. Anderson, MD, a professor at Georgetown University Medical Center and the study’s lead researcher, said in a press release.
Huntington’s is caused by an inherited mutation in the huntingtin (HTT) gene, due to expansions of DNA repeats (CAG) within the gene. Its inheritance is autosomal dominant, which means that only one mutated copy — inherited from one parent — is sufficient to cause the disease. Thus, every child of a parent with Huntington’s has a 50% chance of inheriting the gene.
Disease onset typically happens in a person’s 30s and 40s. In more rare cases, onset occurs during childhood or adolescence, or even after the age of 80. The age at onset depends on the number of times the DNA repeat is expanded. The longer this expansion, the earlier the symptoms of the disease.
Noting that as many as 90% of individuals who have a parent with Huntington’s choose not to take a gene test, a team of researchers at Georgetown University Medical Center sought to find out why.
“Understanding the ‘why’ matters as new clinical trials testing therapies for people who haven’t yet developed symptoms of Huntington’s disease require participants to be tested for the HD gene to be included in the trials,” the investigators said.
The team queried 733 potential Huntington’s mutation carriers enrolling in a clinical trial about the reasons why they chose not to know their gene status. That trial, the Prospective Huntington At-Risk Observational Study (PHAROS) study, (NCT00052143), was carried out between 1999 and 2008 at several sites in the U.S.
As part of this study, participants gave consent for genetic testing with the condition they would not be told the results.
Most of them said the major reasons they chose not to undergo genetic testing were the lack of an effective cure or treatment (66%) and their inability to undo the acquired knowledge (66%).
Many were not concerned about the length of the testing process (61%) or the burden of participating in the test (59%). A majority — 56% of participants — felt optimistic that a treatment to improve symptoms would be developed within the next 10 years, while 53% believed therapies to delay disease onset would appear within that same time frame.
However, some (36%) were less sure about the prospects for a treatment that could completely prevent Huntington’s disease from developing.
“This study shows us that, as new treatments develop that will require genetic testing for clinical trial participation, we should reassess attitudes about how people at risk for disease approach this life-altering choice. It tells us that we should understand, and respect, decisions not to have that testing,” Anderson said.
Understanding why people chose not to take the test also makes it easier for physicians and genetic counselors to bring up the subject with individuals at risk, especially if they are considering a clinical trial, she added.
“These data can promote understanding of how to counsel and support those who consider genetic testing for HD, by increasing knowledge about factors that go into this complex decision,” the researchers said.
As many subjects worried for the lack of a cure or effective treatment, this suggests they should not undergo testing only to participate in clinical trials, which may provide no benefit in slowing disease or treating symptoms, the team said.
This is becoming increasingly important “as individuals are confronted with or reconsider the decision not to test, particularly if required to do so to participate in a promising treatment study,” the researchers added.