Huntington's disease is unique in that a person may know in advance that they will develop the disease, yet there is no way to prevent it. However, people living with Huntington's disease should not be considered hopeless cases. They can receive specialized care at the Huntington's Disease Coordination Center, where a multidisciplinary team provides comprehensive management using the latest diagnostic and treatment approaches. We spoke with Neringa Tutlienė, Coordinator of the Huntington's Disease Coordination Center at Vilnius University Hospital Santaros Clinics, about Huntington's disease, diagnostic testing, and current treatment options.
What Is Huntington's Disease and How Common Is It?
Huntington's disease is an inherited neurodegenerative disorder characterized by three main groups of symptoms: motor, cognitive, and psychiatric disturbances. The disease is caused by a mutation in a single gene. Specifically, it results from an inherited mutation in the huntingtin (HTT) gene located on chromosome 4. This gene is responsible for producing huntingtin, a protein essential for normal brain function. When the gene is mutated, production of the protein is disrupted, leading to the progressive degeneration of nerve cells in specific regions of the brain.
Huntington's disease follows an autosomal dominant pattern of inheritance. This means that if one parent has Huntington's disease, carrying the mutated gene, each child has a 50% chance of inheriting it. Individuals who inherit the mutated gene will inevitably develop Huntington's disease during their lifetime, whereas those who do not inherit the mutation will not develop the disease. In rare cases, the mutation occurs spontaneously rather than being inherited from either parent. It is estimated that approximately 1–3% of Huntington's disease cases are sporadic.
Huntington's disease is a rare disorder, affecting approximately 1 in every 10,000–20,000 people. The prevalence varies slightly between geographical regions. Men and women are affected equally. Although Lithuania does not have a national registry for Huntington's disease, molecular genetic testing has identified approximately 200 individuals carrying the disease-causing mutation. However, this does not necessarily correspond to the current number of patients, as some individuals may have died, while others carry the mutation but have not yet developed symptoms.
The clinical course of Huntington's disease is divided into the following stages:
- Pre-symptomatic (pre-HD) – no clinical symptoms;
- Stage 1 – prodromal stage, characterized by early personality changes and cognitive impairment;
- Stage 2 – early stage, with the appearance of initial motor symptoms;
- Stage 3 – moderate stage;
- Stage 4 – advanced stage;
- Stage 5 – severe stage.
What Are the Most Common Early Symptoms of Huntington's Disease?
A person is born with the mutated huntingtin gene, but the disease does not manifest immediately. In most cases, the first symptoms appear between 35 and 45 years of age. A less common form of the disease is juvenile Huntington's disease (Westphal variant), which affects children and young people younger than 20 years of age. This form accounts for approximately 5–12% of all cases. Juvenile Huntington's disease usually follows a somewhat different and often more severe clinical course. The disease rarely develops before the age of 10 or after the age of 70.
There are three principal groups of symptoms: motor impairment, cognitive dysfunction, and behavioral or personality changes. The earliest manifestations often go unnoticed because they primarily affect emotions and personality. Ten to fifteen years before obvious movement disorders appear, subtle personality changes may develop. Individuals may become slower to react, emotionally different, more irritable, suspicious, anxious, impulsive, apathetic, or depressed. Family members often notice these changes but rarely associate them with Huntington's disease. Consequently, both in Lithuania and worldwide, the diagnosis is most often established only after motor symptoms become evident. Even during the early stages of the disease, productivity declines, along with the ability to participate fully in family life, social activities, and leisure pursuits. Patients gradually lose the ability to recognize emotions, carry out goal-directed activities, prioritize tasks, and organize their daily lives.
During the early stage of the disease, the first motor symptoms may also emerge, including restlessness and clumsiness, followed later by subtle involuntary movements involving the face and limbs.
What Other Symptoms May Develop as the Disease Progresses? What Are the Late Manifestations of Huntington's Disease?
Huntington's disease profoundly affects motor function. One of its hallmark features is chorea, characterized by repetitive, rapid, involuntary, jerky movements involving the limbs and the entire body. Initially, these movements are subtle and may affect only the fingers or hands before gradually spreading to other parts of the body. As the disease progresses, chorea becomes more frequent, generalized, and pronounced. Involuntary movements of the face and tongue eventually interfere with eating, balance, and coordination, increasing the risk of falls. These involuntary movements may also occur during the night, making it difficult to fall asleep and disrupting sleep quality. As chorea advances, patients gradually lose their independence and eventually become unable to walk, care for themselves, or eat independently.
In addition to chorea, Huntington's disease may present with dystonia, gait abnormalities, and impaired coordination. Eye movements, swallowing, and speech may also become affected. During the late stages of the disease, muscle tone often increases, resulting in rigidity, stiffness, and akinesia, replacing the previously dominant involuntary movements.
Another major group of symptoms involves cognitive impairment. Although cognitive deficits may be present from the onset of the disease, they are often subtle and, like behavioral and personality changes, may go unrecognized. Cognitive symptoms include reduced intellectual functioning, impaired attention and memory, psychomotor slowing, dementia, psychosis, and hallucinations.
In Huntington's disease, cognitive impairment primarily affects executive function, decision-making, attention, and memory. Speech gradually becomes less fluent, making it increasingly difficult for patients to find the words needed to express their thoughts. As the disease progresses, intellectual decline becomes more pronounced, and interests become increasingly restricted. Patients gradually lose interest in previously meaningful activities, struggle to learn new information, and find it increasingly difficult to cope with work and everyday household tasks. It should be noted that memory remains relatively preserved during the early stages, whereas aphasia, agnosia, and apraxia gradually develop. Over time, the spectrum of cognitive impairment widens, ultimately progressing to dementia, which develops insidiously and advances gradually.
Depression is the most common psychiatric disorder associated with Huntington's disease. It is important to understand that depression is not merely a psychological reaction to receiving the diagnosis or to knowing that the disease is currently incurable. The disease itself contributes to depression through pathophysiological changes in the brain. Personality changes and depression interfere with social functioning and make it more difficult to provide appropriate care. Patients with apathy often lack motivation and do not seek medical help. In some cases, they even refuse medical consultations, despite their family members' attempts to persuade them. Because depression in Huntington's disease is frequently accompanied by suicidal ideation, appropriate treatment of depression is essential.
What Other Symptoms, Besides Motor, Cognitive, and Behavioral Changes, May Indicate Huntington's Disease?
It is important to recognize that, in addition to motor, cognitive, and behavioral or personality changes, Huntington's disease also affects the autonomic nervous system and multiple organ systems. This may manifest as excessive sweating, urinary dysfunction, gastrointestinal disturbances, sleep disorders, increased or decreased appetite, and an accelerated metabolic rate resulting in marked weight loss that may progress to cachexia. Weight loss occurs not only because of increased metabolism but also because involuntary movements substantially increase energy expenditure. Consequently, regular weight monitoring, dietary counseling, and ongoing nutritional support are important aspects of patient care.
Huntington's disease has also been shown to affect skeletal muscle, causing muscle fiber loss as a result of metabolic disturbances. The disease may involve the myocardium and cardiovascular system and, in men, may lead to testicular atrophy and erectile dysfunction. In other words, Huntington's disease is a multisystem disorder that extends well beyond motor and cognitive impairment.
Autonomic nervous system dysfunction most commonly develops during the advanced stages of the disease but may also appear among the earliest clinical manifestations, even preceding motor symptoms.
What Types of Patients Do You See at the Huntington's Disease Coordination Center? What Symptoms Usually Lead Them to a Neurologist?
Most patients initially seek medical attention because of movement disorders, particularly involuntary movements that they themselves often do not notice during the early stages. The first signs are usually recognized by family members or other close individuals, who encourage patients to seek medical evaluation. Patients themselves are more likely to consult a physician when motor symptoms begin to interfere with their professional activities or are noticed by employers.
Early emotional and cognitive changes often remain unrecognized. Such changes are frequently attributed to personality traits rather than disease. Family members may notice that a person has become more irritable, emotionally distant, or has lost interest in previous activities but assume these are simply changes in character. Currently, there are no universally accepted or validated assessment tools capable of clearly distinguishing normal personality changes from pathological ones.
Where Should Patients Be Referred for Huntington's Disease Diagnosis? What Should Family Physicians Know?
Family physicians should always pay close attention to motor symptoms as well as changes in behavior, personality, and cognitive function. As mentioned earlier, these changes are often reported by family members rather than by the patients themselves. Taking a detailed family history is essential. Physicians should ask whether there have been any family members diagnosed with Huntington's disease or individuals who experienced involuntary movements, died by suicide, or had significant psychiatric disorders.
When Huntington's disease is suspected, the family physician may refer the patient to the Medical Genetics Center at Vilnius University Hospital Santaros Clinics, where the diagnosis can be confirmed through molecular genetic testing. However, involuntary movements, mood disturbances, memory impairment, and personality changes are not specific to Huntington's disease alone. The differential diagnosis is broad. If there is diagnostic uncertainty, the patient should be referred to the Huntington's Disease Coordination Center for consultation with a tertiary-level neurologist.
Another important consideration is that approximately 3% of Huntington's disease cases occur without a positive family history. These represent sporadic mutations, meaning the disease may appear for the first time within a family. Therefore, Huntington's disease should never be excluded solely because there is no known family history. Every patient presenting with involuntary movements should be evaluated by a neurologist, who can refer the patient for genetic testing if Huntington's disease is suspected.
Diagnosis of Huntington's Disease: Where Should the Evaluation Begin? Is Genetic Testing Necessary?
As mentioned previously, the diagnostic process begins with obtaining a detailed medical history, followed by a comprehensive neurological examination. The neurologist determines whether brain computed tomography (CT) or magnetic resonance imaging (MRI) is required.
The diagnosis of Huntington's disease is confirmed by genetic testing. Genetic testing may be performed not only to confirm the diagnosis in symptomatic patients but also in adult family members to determine whether they carry the mutated huntingtin gene. Predictive testing may be offered to siblings or parents of affected individuals who are at least 18 years of age.
Before predictive genetic testing, psychological assessment is mandatory. The psychologist evaluates whether the individual is emotionally prepared to receive potentially life-changing information and whether there are underlying psychiatric conditions that could complicate the process. It is generally recommended that approximately one week elapse between the psychological consultation and genetic testing, allowing the individual sufficient time to consider whether they truly wish to undergo testing. Psychological support is also provided after the test results are disclosed.
Huntington's Disease Is Incurable – What Can Be Offered to Patients?
The primary goals of treatment are to improve quality of life, alleviate symptoms, and slow functional decline. Long-term multidisciplinary care involving specialists from several medical disciplines is often required.
At the Huntington's Disease Coordination Center, patients receive comprehensive care from a multidisciplinary healthcare team that includes a neurologist, psychiatrist, psychologist, medical geneticist, rehabilitation physician, physiotherapist, speech and language therapist, dietitian, and social worker. Psychiatric evaluation is particularly important because psychiatrists can prescribe antidepressants, antipsychotic medications, or mood stabilizers when indicated. Although no disease-modifying treatment is currently available, maintaining motivation to preserve health and actively seeking appropriate care remain essential. Patients who have already been diagnosed are encouraged to attend the Coordination Center, where access to comprehensive multidisciplinary care—including speech therapy, physiotherapy, nutritional counseling, and other supportive interventions—has expanded considerably.
Although Huntington's disease cannot currently be cured, many of its symptoms can be effectively managed. Depression can be treated, irritability and aggression reduced, sleep disturbances addressed, weight loss managed, chorea and other involuntary movements controlled, and impairments in mobility and physical function alleviated. Pharmacological treatment of chorea is generally indicated when involuntary movements interfere with occupational functioning, result in physical injury, cause significant social stigma, impair balance, or disrupt sleep.
Tetrabenazine has proven effective in reducing chorea. In Lithuania, this medication has been included in the List of Reimbursable Medicines since 2015, with 80% reimbursement. Treatment usually begins with a low dose, which is gradually increased as needed. Tetrabenazine is not recommended for patients with severe depression or certain other psychiatric disorders. After treatment is initiated, patients are carefully monitored for adverse effects and treatment tolerability. In clinical practice, tetrabenazine has demonstrated good therapeutic effectiveness.
Genetic Testing Allows the Disease to Be Identified Before Symptoms Develop. What Preventive Measures Can Be Taken After Detecting a Huntingtin Gene Mutation?
Unfortunately, even if a person knows they carry the mutation, the disease cannot currently be prevented. Individuals who inherit the mutation will eventually develop Huntington's disease. However, research suggests that both physical and cognitive activity may modestly delay disease onset, slow progression, and alleviate symptoms. In the TRAIN-HD clinical trial, 25 participants completed supervised exercise sessions three times per week for eight weeks. Motor symptoms and participants' ability to maintain regular physical activity were evaluated, and the results demonstrated beneficial effects on motor function.
Neuronal degeneration begins approximately 10–15 years before the appearance of clinical symptoms, resulting in progressive brain atrophy. During this preclinical period, the formation of new neuronal connections is particularly important. This process is regulated by biologically active substances whose levels increase during physical activity. Therefore, individuals found to carry the mutated huntingtin gene are encouraged to engage in regular physical exercise, participate in sports, and maintain cognitive activity through reading, learning, solving crossword puzzles, and similar mentally stimulating activities, as these measures may help slow neurodegeneration.
Will a Treatment That Alters the Course of Huntington's Disease Soon Become Available?
Researchers around the world are actively working to develop disease-modifying therapies. Particular attention is focused on approaches designed to suppress or silence the expression of the mutated huntingtin gene.
Thank you for the interview.
Interview by Natalija Voronaja
Neurology News supplement of the journal
Internist 
