Deciding whether to pursue testing for Huntington’s disease (HD) can be difficult. This progressive, fatal disease is devastating to individuals and families with each child of a parent with HD having a 50/50 chance of inheriting the condition.
Genetic testing for HD is often carried out through one of the nation’s 80 HD specialty centers. When paired with an expert InformedDNA HD genetic counselor, patients, and at-risk family members receive guidance and support before, during, and after testing, regardless of geographic location or ability to travel.
Understanding Huntington’s Disease
HD is an inherited neurodegenerative disorder caused by genetic abnormalities in a gene called huntingtin (HTT). This gene contains a stretch of DNA composed of repeats of three DNA building blocks C, A, and G (CAG), known as a trinucleotide repeats. Individuals who do not have HD typically have less than 26 of these repeats and individuals affected with the condition have 40 or more. However, as with many genetic disorders, the complexity of the genetics of HD is more intricate than this.
Genetic Testing Complexities
Targeted genetic testing is used to determine the number of CAG repeats in the HTT gene. We all typically have two copies of each of the approximately 20,000 genes in our bodies; one from our mother and one from our father. Individuals with HD have a higher than the typical number of CAG repeats in one copy of their HTT genes. The number of CAG repeats can provide information on who is at risk of developing symptoms of the condition and who is at risk of having a child that could develop the condition.
- Normal: A normal HTT gene that carries no risk of HD has 26 or fewer CAG repeats.
- Intermediate: An HTT gene with 27-35 repeats means the individual will not develop HD; however, an HTT gene with an intermediate number of CAG repeats is unstable and the number of repeats may increase as the gene is passed to children. This means children in the next generation could develop HD.
- Reduced penetrance: For those with CAG repeats of 36-39, it is uncertain if they will develop HD and they may or may not live their life without any symptoms. An HTT gene within this range is also unstable and children may inherit an expanded number of CAG repeats within the HTT-positive, full penetrance HD range.
- Full penetrance: A test result over 40 CAG repeats means the person is HTT-positive and almost certain to develop HD. In general, the longer the CAG repeat region, the earlier disease onset will be.
- Genetic testing for HD can be carried out for different reasons:
- Confirmatory and diagnostic testing
- Pre-symptomatic or predictive testing
- Preconception testing in the setting of in-vitro fertilization (IVF) coupled with preimplantation genetic diagnosis (PGD)
- Prenatal testing
- Asymptomatic children are not routinely tested for HD, even if they are at risk of having inherited the condition. Their autonomy is respected so that they can be allowed to make the decision whether to test for themselves when they are adults.
The Important Role of Genetic Counseling
InformedDNA connects patients to its highly skilled and empathetic genetic counselors. We provide telephone-based sessions, which can remove barriers to getting counseling from a true expert. The implications of genetic testing, including the emotional impact are explored from the comfort of the patient or family member’s home or familiar surroundings.
The relationship with an InformedDNA genetic counselor begins with a 60-90-minute initial consultation to better understand the patient’s goals and motivations for pursuing genetic testing at this time in their life. In this exploratory conversation, the genetic counselor covers many topics. They not only review the benefits and potential drawbacks of test results and their implications for patients and their families, but also explore:
- Potential impact on family and personal relationships
- Financial planning considerations
- Long term care decision making
- Potential need for a living will and/or power of attorney
- Risks and implications for family members
- Reproductive decision making
- The Genetic Information Nondiscrimination Act (GINA), providing clarity on the nuances of this Act and the protections it affords
The majority of people at risk for HD do not ultimately pursue genetic testing for the disease, in part due to the lack of effective treatment and also because they can’t “unlearn” the information once received, according to a recent study. In fact, as many as 90% of individuals who have a parent with HD choose to forego testing and counseling. One thing to note is that an individual can benefit from the counseling portion without the testing aspect. Either way, InformedDNA’s counselors are experienced, board-certified, licensed across the country, and ready to serve patients who do seek their expertise.
Because a genetic test result can be an emotional hit, whether it is normal, intermediate, reduced penetrance, or a full penetrance result, genetic counselors are trained professionals who are both there with and for patients as they learn to navigate their new normal — prepared to offer informed recommendations for dealing with the wide range of feelings and responses.
Let’s consider two scenarios:
- Normal results: Perhaps it seems surprising that some at-risk individuals who discover they have a normal HTT gene face emotional and psychological challenges. They may at first be overjoyed and relieved, however, some individuals over time experience “survivor guilt”; for example, where they have escaped a future with HD but a sibling does not. Others may struggle with readjusting their thoughts of the future they were convinced they were facing, a mindset that may have haunted them for years.
- Full penetrance results: Patients with a positive genetic test confirming they will develop symptoms of HD can experience many feelings, including anger, sadness, grief and despair. Some individuals feel that their fears have been validated, while others jump to planning and organizing as a way of coping. Almost all patients have many questions; where do I go from here? How do I tell my family and my kids? Should I tell my boss? Are there any clinical trials? How do I choose a healthcare team? Who can help with advance care directives? Where can I find support? How do I make long-term care plans? Each question is unique and personal and addressed with empathy. Given the magnitude of the information delivered at a results appointment, subsequent follow up appointments are often scheduled a few weeks out to address any additional questions the individuals or their loved ones may have. InformedDNA genetic counselors are also able to direct patients to support resources, be it at the national or local level, including direction on where to find clinical trials and HD research participation opportunities.
InformedDNA genetic counselors empower patients to make exceptionally personal and difficult decisions regarding their healthcare at a time when they may feel their most vulnerable.
“I can’t thank you enough for being a part of this with us. You said the right things at the right time and were not afraid to ask the tough questions and make us think deeper and talk through more what we thought we were feeling. Your tender heart, kindness and compassion, all your insights, experience, and useful things to think about or strategies to talk about or think about. Thank you is just not enough!”
–Actual patient quote
InformedDNA counselors help each patient understand their inherited genetic risks and provide counseling according to individual needs. Discussing genetic risks with a trained counselor can bring great ease and comfort regarding health concerns large and small. Perhaps most importantly, genetic counselors empower patients to receive the personalized healthcare they need and deserve.
About the author: Claire Egan, M.Sc. CGC, is a senior genetic counselor at InformedDNA. She graduated from Sarah Lawrence College in 2012 with a master’s in Human genetics and has worked in genetics clinics at both New York Presbyterian Hospital, NY, and Children’s Hospital of Colorado. Since joining the specialty genetics team at InformedDNA in 2017, Claire has developed additional expertise in the genetics of neurodegenerative disorders. She provides expert pre-and post-test genetic counseling for a range of neurodegenerative and neurodevelopmental disorders, to patients across the lifespan.