Testing for an incurable disease: points you MUST consider

In the era of genomic medicine, genetic testing is readily available for hundreds of inherited conditions. Insights from testing can include information about ancestral origins, hidden health risks, and reproductive risks. However, while access to genetic testing in the United States is widely available to patients and providers, the decision to undergo testing can be deeply personal. Those who are considering genetic testing need to have a good understanding of what information they may learn, and how it could impact their health and life goals. This is particularly true for genetic testing for Huntington disease, which is incurable.

What is Huntington disease?

Huntington disease (HD) is a severe, inherited condition that affects the brain and nervous system. Symptoms generally appear in the fourth or fifth decade of life (although onset may be earlier) and become significantly worse over time. HD has an insidious onset with patients often first presenting with minor neurological and cognitive signs as well as behavioral and psychiatric changes, such as depression and irritability. Early in the course of the disease, patients may experience minor changes in coordination and chorea. These abnormalities in movement will eventually progress to the point where the patient can no longer speak or care for themselves and becomes totally dependent, requiring full-time care. The median survival is typically 15 to 18 years after the onset of symptoms and the average age of death is 55. https://www.ncbi.nlm.nih.gov/books/NBK1305/#huntington.Summary)

Who can develop Huntington Disease?

Huntington disease has long been known to run in families. It was first described by George Huntington in 1872 and the gene associated with the condition, known as HTT, was identified in 1993. HD is inherited as an autosomal dominant trait and therefore an affected individual has a 50% chance to pass on the causative gene to a child. Since the onset is later in life, many people do not exhibit symptoms until after childbearing years.

Within the HTT gene, there is a repeating sequence of three nucleotides (CAG). This is present in all individuals, however, those with HD have an expansion in the number of CAG trinucleotide. The number of CAG repeats not only determines if an individual is affected but can predict to some degree the severity of symptoms and age of onset. Unaffected individuals have 26 or fewer CAG repeats, resulting in a stable gene that will not increase in size as it is passed on through generations. Someone having 27-35 CAG repeats is not expected to develop obvious symptoms of the disease, but it may expand as it is passed on, causing HD in future generations. HHT genes with 36-39 CAG repeats have reduced penetrance. This means that some people with alleles in this size range will never go on to develop symptoms and others will develop classic HD symptoms. When 40 or more CAG trinucleotide repeats are present, it is fully penetrant and anyone who inherits an allele in this size range will develop symptoms of HD.

What to consider before genetic testing for Huntington Disease?

Genetic testing for HD examines the number of CAG repeats a person has within the HTT gene. Testing is very accurate and can confirm a diagnosis in someone who has symptoms. People with a known family history of HD may also consider genetic testing before they have symptoms, known as pre-symptomatic testing. There is much to consider before pursuing pre-symptomatic testing for HD.

• There is currently no cure or preventive treatment for HD. Some people seek out possible research or clinical trial opportunities if they discover they are positive. Those at risk face the difficult choice of whether to pursue pre-symptomatic genetic testing or not, and having a personal support system in place is very important.
• The average age of onset is 45, but this varies, with about a quarter of all individuals with HD presenting after 50. This can be particularly difficult for patients because often they have just started careers, marriages and family planning.
• Some people decide to pursue testing to lessen their anxiety about not knowing their own genetic status. Prior to testing, individuals need to explore their feelings regarding either result outcome, positive or negative, and have access to a personal support system. While many people feel relieved when getting a negative result, they may not be prepared to psychologically cope with a positive result. Strong feelings can occur regardless of the outcome.
• Test results may impact relationships with family and friends. For some people, knowing their CAG repeat status can help them make important decisions involving family planning and life goals. On the other hand, testing positive for HD may predict the genetic status of other family members, whether or not they want to know.
• A positive result may affect a person’s ability to get certain types of insurance. Currently, there are some legal protections in place for those obtaining health insurance. However, these genetics non-discrimination laws do not apply to life insurance or long-term care policies.

The Huntington’s Disease Society of America (HDSA) recommends that those considering pre-symptomatic testing be seen at a genetic testing center that follows the specific HDSA guidelines. There are a number of these centers across the country where testing procedures may involve several sessions with genetic counselors as well as other professionals from multiple specialties. Each individual’s decision on whether to pursue testing or not is deeply personal and there is no single correct choice. More information about testing guidelines and genetics clinics can be found at HDSA.org; NSGC.org and ACMG.net.

Should children be tested?

Testing is generally not recommended, nor available, for asymptomatic children under the age of 18 because:

• There is currently no effective medical treatment or management for Huntington disease.
• Not all people wish to learn this information and testing a child takes away their ability to choose for themselves.
• Professional societies, such as the American College of Medical Genetics and Genomics (ACMG), National Society of Genetic Counselors (NSGC), and the American Academy of Pediatrics (AAP) all support the professional recommendation to defer genetic testing for adult-onset conditions until a child reaches adulthood.

The era of genomic medicine offers an abundance of testing and personal information. Pre-symptomatic testing for HD has enabled many at-risk individuals to eliminate uncertainty about their future and make appropriate life and reproductive plans. For some couples at risk of having a child with HD, preimplantation genetic diagnosis (PGD) may be an option. This involves in vitro fertilization using the couple’s own embryo that has tested negative for HD. However, some people do not wish to know what their future will hold. The decision on whether to undergo genetic testing for a disease that does not yet have a treatment or cure is deeply personal. Testing for Huntington disease is available through Quest Diagnostics, a leader in genetic testing, and is in-network with over 95% of insurance plans. This can help to ease the burden of worrying about cost and coverage when making an already difficult decision. Quest Diagnostics also has Genetic Counselors with expertise in molecular and neurogenetic testing who are available to help answer any questions providers might have before and after testing. They can be reached at 1.866.GENE.INFO (1.866.436.3463) or GENEINFO@QuestDiagnostics.com.