Author and Contributing Experts to this Guide include:
Huntington's disease (HD) is a rare progressive genetic disorder in which nerve cells in certain parts of the brain degenerate over several years. It affects patients mentally and physically, and while symptoms can be treated, there is no cure, eventually resulting in death.
What is Huntington's Disease?
HD is a neurodegenerative disease, which means it attacks nerve cells. It's mostly hereditary by nature, passed from one generation to the next, although there are a few rare cases where it occurs spontaneously with no known family history.
Adult-onset is the most common form of HD. People with this form usually develop symptoms in their 30s or 40s 1. Early symptoms may include small involuntary movements, mood changes, cognitive issues, and problems making decisions.
Many people also develop involuntary twitching or jerking movements known as chorea. As symptoms progress, people have trouble walking, speaking, swallowing, and performing simple daily living tasks.
A less common form is early-onset HD, sometimes called juvenile HD, which affects a small number of people and typically begins in childhood or a person’s teen years.
HD progresses slowly, resulting in a lifespan of anywhere from 10 to 25 years after a person has been diagnosed. The juvenile form progresses much quicker, resulting in patients passing away in ten years or less.
While doctors can treat symptoms, there’s no way to stop the progression of HD at this time.
HD affects an estimated 3 to 7 per 100,000 people of European ancestry, and is less common in some other populations, including people of Japanese, Chinese, and African descent. Overall, about 41,000 Americans have symptoms of HD, and another 200,000 are at risk of inheriting it.
What Causes Huntington's Disease?
Huntington’s disease is caused by an expanded repeat of the nucleotides “CAG” in the huntingtin gene (HTT) on the short arm chromosome 4. The HTT gene provides instructions for making a protein called huntingtin. This protein appears to play a key role in the brain’s nerve cells, also known as neurons.
Everyone has the HTT gene with a section of CAG repeats. For individuals with Huntington’s disease, this repeat occurs more times than it should for normal function. Typically, this section of DNA repeats about 10 to 28 times. However, in persons with HD, it repeats anywhere from 36 to 120 times.
Ultimately, the series of replications creates a protein strand that's too long for the body to handle. When this happens, the abnormally long protein gets cut up into fragments. However, these fragments are harmful and end up sticking together and clogging up the neuron. This causes cells to die off and triggers the progression of HD.
When an individual with Huntington’s disease has a child, there is a 50% chance that their child will also have HD. Sometimes, when the repeat is passed on to the child, it will accumulate more repeats. This is called anticipation and is most commonly seen when the harmful copy of HTT is passed on from the father. This is important because there is a correlation between the number of repeats and the age of symptom onset.
“All individuals have two copies of the Huntington's gene and when one of those copies is larger than it's supposed to be, or it gets expanded, the gene is unable to work properly. That's what then causes the symptoms of the condition to be able to appear,” explained Fallon Brewer, a lead genetic counselor at the University of Alabama at Birmingham.
“Everyone with the expanded allele will develop symptoms at some point, sometimes not until their forties or fifties or sixties, and maybe even later. Many times, people have had children well before knowing that they have this condition themselves. They're just not symptomatic. Even though it's something they were born with and had their whole life, it takes many decades in most cases for those symptoms to show up,” she added.
Huntington’s disease is inherited in an autosomal dominant inheritance pattern. This means that a person needs only one copy of the gene with a harmful expansion to develop HD.
That means if one of your parents has HD, you have a 50% chance of inheriting the expanded gene. If you get the gene from your parents, you can pass it on to your children, and they will also have a 50% chance of developing HD.
If you don’t get the expanded gene from your parents, you can’t pass it on to your children.
Individuals with 27 to 35 CAG repeats will not have any symptoms of HD but are at risk of passing down a larger repeat to their children. When someone has 36-39 CAG repeats they fall into a grey area. These individuals are said to have reduced penetrance, meaning that while they do carry an expanded copy of the HTT gene, they may or may not show signs or symptoms. If someone inherits 40 or more repeats then they will develop HD at some point in their life. People with the juvenile form of HD tend to have more than 60 repeats.
The Stages of Huntington's Disease
Most researchers believe the severity of the disease and how quickly it progresses are linked to the number of CAG repeats in the HTT gene.
Patients with fewer CAG repeats show symptoms when they are older. They also have a slower progression and reduced symptom severity. This will impact how long each stage of the disease lasts in individual patients.
Huntington’s disease is divided into stages of disease progression.
Stage 1: Early Stages
During the early stage, after a patient has been diagnosed with Huntington’s disease, they are typically able to continue working and engaging in typical activities. They might notice some clumsiness, abnormal eye movements, changes in attitude, and psychiatric manifestations such as anxiety or depression.
Stage 2: Middle Stage
During the middle stages, chorea, which is the irregular and involuntary movements, begin to play a larger role in day-to-day life. This change in movement coupled with general weakness, and increased difficulty speaking and swallowing leads to a decrease in the ability to complete everyday tasks. This can lead to patients leaving their jobs, but they can still continue to complete self-care tasks. In addition to the physical changes, there can be an increase in aggressive behaviors and general changes in social functioning.
Stage 3: Late Stages
During the late stages of HD, the patient is dependent upon caretakers. The patient will often experience significant weight loss and no longer be able to walk or speak. At this stage swallowing can be very challenging and there is a serious risk of choking.
This stage is also characterized by periods of confusion and screaming. Psychiatric symptoms may occur but are harder to recognize and treat late in the disease because of communication difficulties.
People with Huntington’s disease usually die 15 to 20 years after the first onset of symptoms. The actual cause of death is usually a complication from Huntington’s and may include pneumonia, heart failure, or infection.
Signs and Symptoms of Huntington's Disease
Different signs and symptoms appear in each stage of Huntington’s disease. These can be further broken down into movement, cognitive, and psychiatric disorders. In about ⅔ of patients, the first first signs and symptoms are cognitive 2.
Which symptoms appear first can vary widely from patient to patient and the severity of each symptom can also vary widely. This means each person’s functional abilities will be different.
The movement disorders can include both involuntary movement problems and impairments in voluntary movements, such as:
- Involuntary jerking or writhing movements, and quick, sudden, sometimes wild jerking movements of the arms, legs, face, and other body parts (Huntington’s chorea). Chorea is present in more than 90% of patients. It becomes more severe during the first 10 years. Movements are always present during waking hours and are worsened by stress.
- Muscle problems, such as rigidity or muscle contracture (dystonia)
- Slow or abnormal eye movements, including head turning to shift eye position
- Impaired or unsteady gait, posture, and balance, including "prancing" and wide walk
- Difficulty with speech or swallowing
- Impairments with voluntary movements — rather than the involuntary movements — may have a greater impact on a person's ability to work, perform daily activities, communicate and remain independent.
- Olfactory dysfunction
- Facial movements, including grimaces
- Slow, uncontrolled movements
- Abnormal movements can lead to falls
“Sometimes you hear Huntington's disease referred to as Huntington's chorea, and that's actually one of the key symptoms in clinically diagnosing someone with this condition,” said Brewer.
“Especially in those earlier stages, our patients, we don't see too much change over those early years. The movement's going to start to get worse generally, will be pronounced. You'll start to have more balance trouble, start to fall more. Mood symptoms may become more prevalent. They may become less manageable,” added Hope Heller, a licensed clinical social worker in the DC Metro area who has been working with the Huntington's disease community for the past 10 years.
All patients with HD will experience cognitive changes that will progressively worsen over time.
Those cognitive impairments can include:
- Dementia that slowly gets worse, including:
- Disorientation or confusion
- Loss of judgment
- Loss of memory
- Personality changes
- Speech changes, such as pauses while talking
- Degeneration of neurons in the caudate and putamen as well as the cerebral cortex
- Difficulty organizing, prioritizing or focusing on tasks
- Lack of flexibility or the tendency to get stuck on a thought, behavior or action (perseveration)
- Regional and whole-brain gray and white matter changes and progressive gray and white matter atrophy many years prior to predicted disease onset
- Language functions are at a diminished level of syntactic complexity and cortical speech abnormalities. Word-finding difficulties are common in the late stages.
- Lack of impulse control that can result in outbursts, acting without thinking and sexual promiscuity
- Sleep and circadian rhythms are disrupted possibly as a result of hypothalamic dysfunction and/or alterations in melatonin secretion
- Loss of neurons in the globus pallidus, subthalamic nucleus, thalamus, hypothalamus, substantia nigra, and hippocampus
- Lack of awareness of one's own behaviors and abilities
- Impaired visuospatial abilities
- Impaired ability to manipulate acquired knowledge
- Slowness in processing thoughts or ''finding'' words
- Weight loss
- Increased appetite
- Disturbed cholesterol metabolism
- Difficulty in learning new information
“Some of the early signs and symptoms can include things like depression and irritability, poor coordination, or trouble learning new information or making decisions. But it's important to know these early symptoms are very nonspecific and they can also be observed in people who do not have Huntington's disease,” said Brewer.
The most common psychiatric disorder associated with Huntington's disease is depression. Sometimes this is difficult to tease apart. Individuals facing this diagnosis are likely to experience anxiety and depression. However, HD associated depression and anxiety appears to be directly related to changes in how the brain is functioning. Some signs of HD-related depression include:
- Feelings of irritability, sadness or apathy
- Social withdrawal
- Fatigue and loss of energy
- Frequent thoughts of death, dying or suicide
Other common psychiatric disorders include:
- Obsessive-compulsive disorder, a condition marked by recurrent, intrusive thoughts and repetitive behaviors
- Mania, which can cause elevated mood, overactivity, impulsive behavior and inflated self-esteem
- Anxiety, stress, and tension
- Bipolar disorder, a condition with alternating episodes of depression and mania
- Behavioral disturbances
- Restlessness or fidgeting
- Psychosis, including affective psychosis, or schizophrenic psychosis
- Intermittent explosiveness, apathy, and aggression
- Alcohol abuse
- Sexual dysfunction and deviations
- Delusions, often paranoid
“The earlier symptoms tend to be largely cognitive or psychiatric and mood-related. Depression and anxiety can be early signs of Huntington's. But I don't want anyone at risk to think that just because they have depression and anxiety that they must be in the early stages," said Heller
“We really look to sort out personality changes and bigger mood changes. If somebody is suddenly more irritable than they used to be, has a shorter temper or suddenly becomes more empathetic, the depression and anxiety really start to sort of spiral out control,” she added.
There is not much difference in the treatment of early psychiatric symptoms that people who have similar symptoms without HD. However, early intervention is critical because treating and managing symptoms early on leads to overall better quality of life, especially for someone in the early stages of HD.
“I get calls from young moms that are at risk or they're gene-positive and find themselves more forgetful or having a harder time managing things. But with a lot going on and as the mother of young children, I caution them because I don’t want somebody that's at risk or knows they're gene-positive to suddenly think, oh my goodness, I'm already showing signs.
“Although there are early signs, you would look for some balance issues such as if you're starting to fall or if suddenly riding a bike is harder. It's a relatively slow progressing disease depending on the general age of onset.
You're not going to see changes over like weeks to months, you're going to sort of see changes over months to years quite often,” added Heller.
Psychiatric issues are an ongoing and troubling concern for healthcare providers.
“You'll see a change in the psychiatric symptoms over time. Sometimes as someone progresses, those do get a little bit better. Sometimes they can get worse. And there's always the concern with impulse control and depression about the high risk of suicide because of impulse control and not having that time to stop yourself,” noted Heller.
There are certain key milestones where those providers are especially on guard.
“In my experience, the first hardest conversation that we have with a patient is the diagnosis. And sometimes the harder conversation is actually the ‘you should not be driving anymore conversation,’” said Heller.
As HD progresses, patients are slower to react and judgment may be impaired because of movements.
“You may be a little jerkier driving. There are lots of factors that play into it and oftentimes the person will say, ‘Well, I have my radio off. I'm very focused.’”
“Quite honestly, it's not about what you are doing while you drive. It's if a kid kicks the ball into the street, is your reaction time fast enough to slam your brakes? If another car cuts you off, is your reaction time quick enough?” said Heller.
Symptoms of Juvenile Huntington's Disease
The start and progression of HD in younger people may be slightly different from that in adults.
Juvenile HD is defined as the onset of symptoms before age 20 years. It accounts for up to 10% of individuals with HD. Severe mental deterioration, prominent motor and cerebellar symptoms, speech and language delay, and rapid decline common in juvenile HD patients.
Early onset symptoms can include:
- Behavioral changes
- Difficulty paying attention
- A rapid, significant drop in overall school performance
- Behavioral problems
- Physical changes
- Contracted and rigid muscles that affect gait (especially in young children)
- Tremors or slight involuntary movements
- Frequent falls or clumsiness
Prevalence and Risk Factors for Huntington's Disease
Huntington's is not a discriminatory disease, meaning it doesn't target one gender or a specific age group, though most are between the ages of 30 and 50 during the onset of symptoms. It all comes down to whether or not someone is carrying a copy of the expanded HTT gene.
“Huntington's disease affects about three to seven per 100,000 people of European ancestry. However, there are some places in South America, like Venezuela for example, where the overall prevalence of HD is about one in 20,000, so it’s a bit more common. A particular area in Maracaibo which is in Venezuela, it's one of the most Northern Lake regions in that country has a much higher prevalence of about seven cases per 100 people,” said Fallon.
Conversely, there are populations in which it's less common such as individuals of Japanese, Chinese or African descent.
Huntington's is very rare in children, and it is not something that happens in young children. If it occurs in children, it's typically onset in the late teens and early 20s and it progresses much quicker than if it was onset in adults.
Diagnosis of Huntington's Disease
Initially, if Huntington’s disease is suspected because of family history, a doctor will start out with a simple questionnaire and a physical to focus on your symptoms. Family history is important, but additional analysis is essential.
Doctors will look for physical symptoms such as changes in your motor skills, balance, and reflexes involving your coordination. You will also be examined for any sensory changes in your mental or psychiatric health.
Abnormal movements and behaviors are one of the telltale signs of Huntington's, so be completely upfront and honest with your doctor about any noticeable changes.
“There are two different pieces to a diagnosis. It's largely a clinical diagnosis and that is different from the gene tests.
“You can go through the genetic testing process and find out if you have the gene mutation and you can be gene-positive and have the gene mutation, but that is not a diagnosis. Just because you've been told you have the gene, you have not been diagnosed. The diagnosis is clinical. It’s based on psychiatric components and motor symptoms,” said Heller.
The medical community disagrees at times on how to officially diagnose HD. And how it’s diagnosed has changed over the years.
“You would see an HD specialist or a neurologist or a neuropsychiatrist and they would look at your symptoms and look at your family history. And if you have a known family history, you could technically receive a clinical diagnosis without testing.
“Before 1993, there wasn't a gene test easily accessible. So people were diagnosed largely on family history and symptoms,” added Heller.
The combination of clinical and genetic testing is now the best course of action for diagnosis.
“It's always good to confirm a diagnosis with genetic testing. And a genetic diagnosis is performed by sending a blood sample from the patient to a lab that offers testing for HD. That testing lab will run an analysis to determine the number of CAG repeats for each of the individual’s Huntington's alleles. So, if one of those repeat numbers is 40 or more, that would confirm a diagnosis of HD,” said Brewer.
The Huntington Disease Society of America (HDSA) offers a recommended testing process targeted for someone who is at risk based on family history, but they themselves are not showing any signs or symptoms.
You can get a genetic test if you have a family history of the disease but don't have symptoms. This is called predictive testing. The test can't tell you when the disease will begin or what symptoms will appear first.
“They go through a predictive testing protocol, which typically involves a genetic counseling consultation, a psychological evaluation, a neurologic exam, and then a blood draw. While steps may vary from center to center or place to place, that's kind of the model that's put forth by the HDSA and recommended to follow,” added Brewer.
A doctor may order brain-imaging tests such as an MRI or CT scans that show detailed images of the brain.
These images may reveal changes in the brain in areas affected by Huntington's disease but may not show up early in the course of the disease. These tests can also be used to rule out other conditions that may be causing symptoms.
Some people with a family history of HD prefer to know their current risk before they begin planning for a family. DNA tests to detect the abnormal HD gene on chromosome 4 can help to prepare you for the future.
A critical part of this is meeting with a genetic counselor so you can discuss and fully understand the pros and cons of testing.
For individuals with the expanded HTT repeat, there are a number of options available for family planning:
- Having children the "old-fashioned" way. There is a 50% chance that the child will inherit the repeat and also develop HD in their future
- For families who want to ensure that their child will not be affected, they could undergo in vitro fertilization followed by pre-implantation genetic diagnosis. Embryos would be screened for the repeat and only embryos without the repeat would be placed in the mother's uterus.
- During pregnancy, an amniocentesis or a CVS testing can reveal whether the fetus has the CAG repeat or not. If the child carries the repeat, then additional options such as termination would be considered.
- Egg donation or sperm donation
As with all types of DNA testing, there are certain strengths and limitations that come along with the results. For example, knowing whether you're a carrier makes it easier to prepare for the future and to educate yourself on the disease and its symptoms.
However, for some individuals, having this information can lead to anxiety. Knowing that later in life you will develop HD, a condition for which there is currently no cure can be frustrating and scary.
For women who are already pregnant, you can test the child through an amniocentesis. After the child is born, it would not be recommended to have the child undergo testing until they were 18 years old. Normally, HD is an adult-onset condition, and it’s not advised to undergo testing until informed consent can be obtained from the individual undergoing testing.
Treatment and Care Options for Huntington's Disease
There is no cure for Huntington’s disease, but there are treatment options to lessen the symptoms.
However, researchers are optimistic to a certain degree.
“While we don't have a cure yet for Huntington's disease, we are getting ever closer. We have symptomatic treatments that can help today and then we're building from a scientific standpoint, things towards a cure that is really hopeful for tomorrow,” said Dr. Victor Sung, a neurologist at the University of Alabama at Birmingham. Sung is the director of the Huntington’s disease clinic, which has been designated as one of the nation’s Centers of Excellence by HDSA.
Dr. Sung added, “Because of the genetic aspects of the disease, I have patients with other diseases like Alzheimer's or Parkinson's disease that have a lot more public notoriety, and certainly a lot more people have those diseases.
“But we don't have a good handle on what the exact cause of Parkinson's disease is or what the exact cause of Alzheimer's disease is. And when you don't have that, it's hard to target a disease and cure it.
“However, for Huntington's disease, we know what the cause is. The cause is that mutated gene and all the things that come out of it. So, it's as simple and as complex as stopping that mutated gene from doing what it wants to do.
And it's funny, back in the early 90s when the gene was finally sequenced, a lot of people felt like back then within 5 or 10 years we're going to have a cure for Huntington's disease. But it's proved a lot harder than that.”
The science and finding a cure for Huntington’s disease has accelerated though. Sung remains realistic about what lies ahead.
“There are multiple disease-modifying or curative type strategies in investigation in human beings right now. We're closer than we've ever been. And I think yes there are exciting things that everyone wants to talk about like CRISPR and things like that. Those are still in animal models are mouse models.
“I'd love for CRISPR to be a reality, but the real truth is that that's further away for humans with Huntington's disease.
“But we have other technologies that are in investigation in human beings with Huntington's disease right now. One of them is in a phase three trial, which is the last step that you need before FDA approval. So that's as close as you can be,” says Dr. Sung.
Until this happens, the best course of action is to treat various symptoms of HD so that patients can live as comfortable as possible after diagnosis.
Because HD affects different aspects of a person's body, there are numerous treatments that doctors may try including, but not limited to:
- Huntington's chorea, which is uncontrollable body movements, is often treated with physical therapy, amantadine and tetrabenazine, though antipsychotic drugs are an option should tetrabenazine not work. Possible side effects include drowsiness, restlessness, and the risk of worsening or triggering depression or other psychiatric conditions. Other drugs that may help suppress chorea include levetiracetam and clonazepam but side effects may limit their use.
- Antidepressants, mood stabilizers, and antipsychotics medications are commonly administered to help with psychiatric disorders caused by Huntington's wherein patients can't control emotional and cognitive changes. Antipsychotic drugs such as quetiapine, risperidone, and olanzapine may suppress violent outbursts, agitation, and other symptoms of mood disorders or psychosis. But these drugs may cause different movement disorders themselves. Mood-stabilizing drugs can help prevent the highs and lows associated with bipolar disorder and include anticonvulsants such as Divalproex and carbamazepine.
- Psychotherapy, speech therapy, and occupational therapy can all help improve the quality of life and limit the amount of outside help a person with the disease needs.
- Speech therapy can help improve the communication impacted by impaired throat and mouth muscles that are essential for speech, swallowing, and eating.
- Physical therapy can help you maintain mobility for as long as possible by teaching you appropriate and safe exercises that enhance strength, flexibility, balance, and coordination.
- Occupational therapy can help the person with Huntington's disease, family members and caregivers on how to use assistive devices such as handrails, and devices for bathing, dressing, eating and drinking.
- Because HD patients have difficulty maintaining a healthy body weight nutritional therapy is also a prescribed course of treatment. Higher caloric needs due to physical exertion or unknown metabolic problems may be the cause and may require three meals a day or use dietary supplements.
- Treatment can also involve engaging support agencies, including nonprofits such as
the Huntington's Disease Society of America or local and state health or social service agencies that may provide daytime care for people with the disease, meal assistance programs or respite for caregivers.
“There are two FDA approved drugs in the United States that will treat the motor symptoms of the chorea of the disease. And those are very effective treatments. There are other medicines that are used off label to treat the motor symptoms of the disease as well,” commented Dr. Sung.
Not all treatments work for all patients. Doctors will prescribe specific treatments as they see fit as symptoms progress. Also, medications will evolve over time, and in some cases, drugs that treat some symptoms may result in side effects that worsen other symptoms.
“There are structural and chemical changes in the brain caused by Huntington's disease, in some ways those behavioral symptoms are treated maybe even more effectively in Huntington's disease than they are saying just with your person on the street who has depression.
“If we can make the behavioral symptoms better, irritability or impulsivity or anger or aggression, depression, anxiety, any of those things are causing a big problem. If we make those better, that can have a huge impact on the patient and family as well,” added Dr. Sung.
During the early and middle stages of the disease when the symptoms are still impactful but not overwhelming, medical treatments such as drugs and therapies can help patients maintain their independence.
Depression and suicide are common among persons with HD. It is important for caregivers to monitor for symptoms and seek medical help for the person right away.
Once the disease hits the late stage, patients will likely need ongoing care either in the home or at a qualified facility.
Prevention for Huntington's Disease
There is no real way to prevent Huntington’s disease after a person has been born. You may be born with the expanded HTT gene or not.
The only way to prevent the disease is through planned genetic testing strategies and family planning options. A genetic counselor can discuss the potential risks associated with HD and ofter alternatives if you are an affected parent.
Couples must decide whether to have children or not, or whether to consider methods such as in vitro fertilization with donor sperm or eggs, or other similar options.
Prognosis of Huntington's Disease
Huntington’s disease is always fatal with an average life expectancy of about 15 to 20 years after an initial diagnosis. Juvenile Huntington's disease usually results in death within 10 years after the onset of symptoms. Coping with a diagnosis and treatment is critical to the quality of life going forward.
Common causes of death from HD include:
- Pneumonia or other infections
- Injuries related to falls
- Complications related to the inability to swallow
The number of CAG repeats may determine how severe symptoms are. People with few repeats may have mild abnormal movements later in life and slow disease progression. Patients with a large number of repeats may be severely affected at a younger age.
“The Huntington's disease community from a support standpoint has a really strong online presence from online support groups to Facebook groups and all these kinds of things. So reach out to the community and you'll really be embraced and they'll help you to get plugged in and then get plugged into the resources that you have locally.
“Between all of the clinical and research organizations for Huntington's disease, there is a reach that covers really most of the United States and really most of the world. So just reach out and find and connect with a center, whether it's a research center or a clinical center, there are people there who can help you,” said Dr. Sung.
“If you want to be a part of the research towards a cure, there are opportunities to participate. There are multiple phase two trials ongoing that hopefully if they're successful will go to phase three in the coming years too. So, there's stuff coming very soon.
“There are lots of opportunities to get involved and lots of opportunities to get help to deal with everything that you're going through now and in the future too. The message is that you're not alone and there are tons of websites where people can find resources where they can get help and get questions answered,” added Dr. Sung.
You can learn more about current ongoing research trials by going to clinicaltrials.gov.
What to do Next: Living with Huntington's Disease
Huntington’s disease progresses over several years and affects each person differently. So living with the condition is going to vary depending on your symptoms and rate of progression.
However, because there is no cure and the condition is fatal, it is essential to anticipate what care will be needed in the advanced stages of the disease. The earlier these discussions take place, the more that the patient can be involved in helping to make these decisions. You should include genetic counseling and your doctor in these discussions so you know exactly what to expect.
Creating end-of-life directives and estate documents can help ease the transition for family members. They avoid conflicts at a later date. Specifically, you will need to address care facilities, hospice care, and the contents of a living will. Advance directives will also need to be addressed so a person can empower the right people to make decisions when they are no longer able.
Also, consider accessing various support groups that can help guide your choices and provide valuable resources over time. There are currently 50 centers of excellence across the United States for Huntington's disease. You can go to Huntington's Disease Society of America to find a center near you.
Huntington's Disease Society of America (HDSA)
505 Eighth Avenue
New York NY 10018
Phone: 800-345-4372 (toll-free); 212-242-1968
Huntington’s Disease Youth Organization
PO Box 6371
Delray Beach FL 33482
Hereditary Disease Foundation
New York NY 10032
Huntington Study Group (HSG)
University of Rochester, HSG Administrative Office
1351 Mount Hope Avenue
Rochester NY 14620
Phone: 800-487-7671 (toll-free)
- Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA, Scahill RI, Wetzel R, Wild EJ, Tabrizi SJ. Huntington disease. Nat Rev Dis Primers. 2015;1:15005.
- Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA, Scahill RI, Wetzel R, Wild EJ, Tabrizi SJ. Huntington disease. Nat Rev Dis Primers. 2015;1:15005.
Brenna: You're listening to the Rare Disease Connection, a production of Aspect Health and raredisease.com. When someone is diagnosed with a rare disease, the effects of that diagnosis are not only in the patient, but their entire family. Today we're going to talk about a condition called Huntington's disease with roughly 41,000 symptomatic Americans and more than 200,000 at risk of inheriting this disease. A diagnosis of Huntington's disease is felt across entire families. For families facing a new diagnosis, you likely have more questions than answers and that's why we're here. The Rare Disease Connection and our additional resources on raredisease.com and yourdna.com brings together the people whose expertise can explain what you're facing. Brenna: From diagnosis to prognosis, to treatment options, all the way to questions like who do I talk to? Where are the people that have been through this before? You'll find those answers here. From doctors, geneticists, academics, genetic counselors, patient organizations, other patients and their families, they're all within your reach and we're here to connect you. This is the Rare Disease Connection. Brenna: Hey everyone, this is Brenna, cohost of the Rare Disease Connection and director of patient education yourdna.com. Today I'm going to bring you conversations with four experts on Huntington's disease. Before we get started, you should know that this podcast is just the beginning. We have taken the information from this podcast and added additional resources, explanations, links and references for you in a downloadable guide. You can get your free copy by going to rare disease.com/huntingtons. That's rare disease.com/huntingtons. So let's get started. Our first conversation is with Fallon Brewer, a certified genetic counselor in Birmingham, Alabama. Thanks so much for joining us today Fallon. So why don't you tell us just a little bit about yourself. Fallon Brewer: Sure. I received my training in genetic counseling at the university of Utah. I'm currently one of the lead genetic counselors at the University of Alabama Birmingham. And my involvement with the Huntington's disease community is primarily providing genetic counseling for individuals pursuing predictive testing for HD. Brenna: How long have you been involved with the Huntington's disease community? Fallon Brewer: About 10 years that I've been doing this. So quite a while now. Brenna: So it seems like you have a wealth of experience. So speaking to that experience as a genetic counselor, what immediately comes to your mind when you hear Huntington's disease? Fallon Brewer: That's a great question. I think there's so many things that come to mind. But I think one that stands out is hope. I believe that there is so much research and so many promising therapies and treatments that are being investigated, whereas previously management was largely symptom-based. I'm hopeful in the near future that the management will be more disease-based, meaning slowing disease progression and ultimately stopping disease manifestations. Brenna: I think that's something that probably everyone's looking forward to. So let's back up just a second. From my understanding, Huntington's is a genetic condition. So what's actually occurring genetically that causes Huntington's? Fallon Brewer: Right. So it is a genetic condition. And Huntington's disease is caused when there is an expanded trinucleotide repeat on only Huntington's allele. So it's specifically a CAG repeat. And we all, all individual have two copies of the Huntington's gene and when one of those copies is larger than it's supposed to be, or it gets expanded, the gene is unable to work properly, and that's what then causes the symptoms of the condition to be able to appear. Brenna: So let's say someone has this expanded allele. They have Huntington's disease. What's the risk for their family members to also have this condition? Fallon Brewer: Right. We get that question a lot and [inaudible 00:04:42] more dominant condition, which means that any individual who was born with HG, whether that person is symptomatic or not, has a 50% chance to pass the condition on. Brenna: So are you saying that some individuals who have this expanded allele are not going to be symptomatic? Fallon Brewer: Everyone with the expanded allele will develop symptoms at some point. But that would be a later onset, sometimes not until the forties or fifties or sixties, sometimes even later. And so sometimes people are already, have made their family planning decisions and had children well before knowing that they have this condition themselves. They're just not symptomatic. Even though it's something they were born with and had their whole life, it takes many decades in most cases for those symptoms to show up. Brenna: So how common is this condition? Are there certain populations that are more likely than others to have Huntington's? Fallon Brewer: Right. So Huntington's disease affects about three to seven per 100,000 people of European ancestry. So that is one of the more common populations. There are some in South America, like Venezuela for example, where the overall prevalence of HD is about one in 20,000, so more common. Even a particular area in Maracaibo which is in Venezuela, it's one of the most Northern Lake regions in that country has a much higher prevalence of about seven cases per 100 people. So there certainly are populations in which it is more common. And likewise, there are populations in which it's less common such as individuals of Japanese, Chinese or African descent. Brenna: So it seems to really vary by ethnicity. Does it tend to vary by gender or socioeconomic class or anything like that? Fallon Brewer: It does not. So men and women are equally affected with this condition. And the economic status does not influence that either. Brenna: I'm curious about how someone actually receives this diagnosis. Are there certain signs or symptoms that would make a physician or genetic counselor suspicious of Huntington's? Fallon Brewer: There certainly are. Some of the early signs and symptoms can include things like depression and irritability, poor coordination or trouble learning new information or making decisions. But it's important to know these early symptoms are very nonspecific and they can also be observed in people who do not have Huntington's disease. So these symptoms don't allow for a clinical diagnosis to be made. There certainly are more influential symptoms that are things like involuntary jerking or twitching. Those movements are also known as chorea. So sometimes you hear Huntington's disease referred to as Huntington's chorea, so there's involuntary movement. And that's actually one of the key symptoms in clinically diagnosing someone with this condition. But as the condition progresses, the movements become a lot more pronounced and individuals may have trouble walking, speaking, swallowing. But there certainly are signs and symptoms that we look for both genetic counselors as well as physicians and other healthcare members who see these patients. Brenna: So I know you're mentioning like a clinical diagnosis. How does someone actually receive that diagnosis? And is there something different than a clinical diagnosis? Fallon Brewer: There is. So a diagnosis of Huntington's disease can be made one of two ways, either clinically, which means based on symptoms that the person is exhibiting. And again, these need to be more of the motor or movement type symptoms that chorea that I was talking about earlier. But it's always good to confirm a diagnosis with genetic testing. So a molecular diagnosis. And a genetic diagnosis is performed by sending ideally a blood sample from the patient to a lab that offers testing for HD. And then that testing lab runs analysis to determine the number of CAG repeats for each of the individuals Huntington's alleles. So if one of those repeat numbers is 40 or more, that would confirm a diagnosis of HD. Brenna: So I know you were talking earlier about how the number of repeats maybe can indicate like when someone might be showing signs or symptoms. So what about someone who isn't showing signs or symptoms but has a parent who was diagnosed with Huntington's disease? If they want to know their status, how do they get those answers? Fallon Brewer: Exactly. So and that's largely what I deal with working with predictive patients in the HD clinic at UAB. There is a process put forth by the HDSA, which is the Huntington Disease Society of America. And that process allows for someone who is at risk based on family history, but they themselves are not showing any signs or symptoms. Then they go through this process or predictive testing protocol, which typically involves a genetic counseling consultation, a psychological evaluation, a neurologic exam, and then a blood draw ultimately for the testing to be done. And so while the steps may vary from center to center or place to place, that's kind of the model that's put forth by the HDSA that's recommended to follow. Brenna: So thinking about the flip side of that, maybe someone just got diagnosed and they're wanting to have a family, what sort of advice would you give for family planning? Fallon Brewer: Yeah, there definitely are options out there for individuals who may find themselves in that position and meeting with a genetic counselor or reproductive endocrinologist could definitely be helpful so that the person can be informed of each of their options and be able to make a fully informed decision that's best for them. Brenna: Now that we've spent time talking about what Huntington's disease is and how someone receives a diagnosis, what's your best advice for someone who is diagnosed with Huntington's or maybe who has a loved one who is diagnosed? Fallon Brewer: Sure. I think HD is a life changing diagnosis, not only for the person being diagnosed, but also for their loved ones and their caregivers. So my advice would be to really try to utilize the resources that are available to them, whether that be a centers of excellence where they are able to be followed by a multidisciplinary team of healthcare providers. Usually that includes neurology, social work, various therapies like physical or speech therapy, psychiatry and others to help manage the symptom usually with medication or altering home accommodations. But by utilizing the team, the family and the patient can be aware of clinical trials and research that they may also be eligible for. So that can definitely be helpful. Fallon Brewer: And I would also recommend trying to participate in a support group for HD. I think for some people feeling connected and being able to network with other families who are on a similar journey can be helpful. So if that's something they feel would be helpful for them, I definitely would recommend seeking out those groups, whether they be physically located near them or there's a lot of different options with technology now to participate in support groups. But most importantly, I would say, don't give up hope there. I said earlier, there's so much promising research being done that hopefully can provide a cure for HD one day. So say hopeful and take advantage of those resources. Brenna: So speaking of those support groups as well as centers of excellence, is there a place that you'd recommend for patients to go to get that information? Fallon Brewer: Yes. So the Huntington's Disease Society of America has a great website. It is hdsa.org. And on that website you can find a centers of excellence near you or if there's not one directly in your state, you can find which one may be closest. They also have a lot of other great resources, just patient information, booklets about the genetics of the condition, about different clinical trials and research being done and other ways to connect. So that website really has a lot of great information. And I think for those who are also trying to, due to reasons whether their insurance requires it or they prefer to go, if they're predictive and need to go through that process, they can also find a genetic counselor near them by going to nsgc.org. And there's a find a counselor button there that can help connect them with someone in their area that can get them plugged in and connected where they need to be. Brenna: Thanks Fallon for taking the time to talk to us today. Whether you've interacted with the genetic counselor yet or not, they play an invaluable role in the journey of anyone diagnosed with a rare genetic disease. If you think you or your family might have Huntington's disease, I would recommend looking at nsgc.com to find a genetic counselor near you. Our next conversation is with Hope Heller. She is a clinical social worker currently working as the clinical director of operations at Georgetown university's Huntington's Disease Care Education and Research Center. Thanks so much for talking to us today. Why don't we start out with you just telling us a little bit about yourself. Hope Heller: My name is Hope Heller. I'm a licensed clinical social worker in the DC Metro area. I have been a social worker for over 10 years now. I've always worked in healthcare. I finished my masters at University of Pennsylvania in 2008 and then I've been working with the Huntington's disease community for a little over 10 years now. I started out as the local chapter social worker doing support groups and resources and I worked at that for about six years. While I was doing that, we opened the first multidisciplinary Huntington's disease center in Washington DC at MedStar Georgetown University Hospital. So I've been at MedStar in the Huntington Center since it opened in 2012. Brenna: So thinking about that experience as a clinical social worker, what immediately comes to mind when you hear Huntington's disease? Hope Heller: I think about the families and the people as individuals. I can give you the laic scientific list of symptoms, but the truth is I think about a person in their family, if you have a parent with Huntington's disease, you have a 50% chance of inheriting it and you have to make all sorts of decisions with that as far as to get tested to not get tested. To me, I always think about there's the piece of the symptoms and the disease and then there's the people and the families and how much they're affected by it. Brenna: So thinking about the diagnosis of Huntington's disease, how does someone actually go about receiving a diagnosis? Hope Heller: Right. So there are two different pieces that I want to make the distinction of. So it's largely a clinical diagnosis and that is different from the gene tests. So just, I'll break it down. At the age of 18, so you're born with the genetic mutation, but once you are 18 you can go into a HD specialty center, go through the genetic testing process and find out if you have the gene mutation. So you can be gene positive and have the gene mutation, that is not a diagnosis. So I always like to make that distinction that just because you've been told you have the gene, you have not been diagnosed. The diagnosis is, it's clinical. So it's based on psychiatric components and motor symptoms. There's back and forth. And I'll be honest, I think it depends on probably what doctors you talk to now. Hope Heller: Typically, at this point we don't diagnose without a certain level of motor symptoms. Some of that is because some of the psychiatric components could be separate from Huntington's disease and that is harder sometimes to tease out. But so you would see an HD specialist or a neurologist or a neuropsychiatrist and they would look at your symptoms and look at your family history. And if you have a known family history, you can technically receive a clinical diagnosis without testing. Before 1993, there wasn't a gene test easily accessible. So people were diagnosed largely on family history and symptoms. Brenna: If they were to look at someone's brain of someone who has Huntington's disease, would there be differences to someone who does not have this condition? Hope Heller: So in the basal ganglia, you're going to start to see more atrophy. That being said, and I've asked the neurologists that I work with many times, it doesn't seem to always be something that's caught on brain imaging. And the explanation I've been given is that if somebody comes into a neurologist without a known family history and a lot of imaging is ordered, that I guess the view or the scan that gets used doesn't always look at the brain and that it's not a picture that's typically taken, if that makes sense. I'll defer that really to the experts. But yeah, you're going to start to see atrophy, especially in the basal ganglia. Brenna: So thinking about someone who might have just received a diagnosis or who might be concerned that they carry the Huntington's disease repeat, then if they were looking to start a family and we want him to make sure they didn't pass this genetic change onto their children, what sort of family planning options would a couple have? Hope Heller: So there's actually like a good variety of options and a lot of people don't know about them. And a lot of people just assume, well I have this gene so I guess I can't have kids. Or if I have kids, I have to put them at risk. So I want to just start before I give any options by saying that I feel very strongly that people should make their own decisions about family planning and that the choice to have kids or not have kids and how you do that is so personal. So we give our patients the options, but we really encourage them to talk to their partner, to talk to their family and really decide what works best for them. So the first option is to have kids the old fashioned way. Now that's not a way to not pass it along. If you just have kids the old fashioned way you have a 50% chance if you have the gene of passing along that gene mutation. There is something called PGD IVF and that is where you go through the process of doing in vitro fertilization. Hope Heller: And once you get to the stage where you have embryos, the embryos themselves are tested for the Huntington mutation. And then only the embryos that do not have the mutation are implanted. For some people it's a concern from religious standpoints and own views of what happens to those other embryos and all the things that go along with IVF. But that is sort of the best way in terms of having your own children with your own DNA with your partner that you're not passing along. I think the process can be 20 to $50,000 or more and it's variable what insurances cover, don't cover. I think most people end up paying largely out of pocket. I believe in the UK, if you do this, you get two rounds of IVF free through their health system, but in the US it ends up being largely out of pocket. Hope Heller: Then depending on if it's the male or the female that are the gene carrier, there's always a donation or sperm donation and then adoption also is an option. The other option is and this comes up is if somebody has largely planned to go through one of these processes or hasn't made a choice about whether or not they want kids because they don't want to pass it along and there is a pregnancy you can test in utero. Again, I am a firm believer that a woman should make her own choices about her body. I have no opinion one way or another about this piece, but the idea behind testing in utero is that if the fetus does test gene positive, then you would not continue that pregnancy. It happens. I think it probably happens more than people talk about and some people choose that option as opposed to other routes because it is less expensive. Hope Heller: But the one thing that I tend to say to people is if this is a child that you want, if you are actively trying to have a baby and this is how you're planning to rule out Huntington's disease, you have to think about how you're going to feel having to make that decision. I think it happens outside of HD where you find out something in a pregnancy and have to make a tough decision. But obviously going into it with HD, there's a 50% chance that that's the answer you're going to get. And we don't want somebody to test in utero, have a child that is gene positive, you know it's gene positive and then you continue that pregnancy. Obviously you can't force somebody to end a pregnancy. But the piece to that is we don't test until somebody is over the age of 18. There is rare cases of juvenile onset HD, but we consider it largely in adult onset disease and therefore we consider it an adult decision to get tested. Hope Heller: There's a lot of ramifications and there's a lot that comes with having that information. So it really becomes an ethical issue for a child to be tested, to know that they're gene positive growing up when they may not have an onset of the disease until their thirties, forties, fifties, sixties. So again, those are sort of the main options as far as having kids. And so what I always say to people is you have to think about what's going to work best for you and your family. But those are important conversations to have. How are we going to do this? How are we going to talk about Huntington's disease with our children? What are the resources? Hope Heller: I'll put a plug right in here for HDO, the Huntington's Disease Youth Organization. HDO really does a nice job talking about the import