Huntington's Disease

A hereditary neurodegenerative disorder that causes progressive breakdown of nerve cells in the brain, affecting movement, cognition, and behavior.

Overview

Huntington's disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. It deteriorates a person's physical and mental abilities during their prime working years and has no cure. HD is known as the quintessential family disease because every child of a parent with HD has a 50/50 chance of inheriting the faulty gene.

The disease is caused by a mutation in the huntingtin (HTT) gene on chromosome 4. This mutation involves an abnormal repetition of the CAG (cytosine-adenine-guanine) DNA sequence. While everyone has CAG repeats in their HTT gene, people with HD have an expanded number of these repeats, typically 40 or more, which leads to the production of an abnormally long protein that damages brain cells.

Named after Dr. George Huntington who first described it in 1872, the disease affects approximately 3 to 7 per 100,000 people of European ancestry. Symptoms typically appear between ages 30 and 50, though they can occur at any age. The earlier the symptoms appear, the faster the disease progresses. HD affects men and women equally and crosses all ethnic and racial boundaries.

Symptoms

Huntington's disease symptoms vary widely between individuals and progress over time. The disease affects movement, cognitive function, and psychiatric well-being. Early symptoms are often subtle and may be overlooked or attributed to other conditions.

Movement Disorders

  • Involuntary jerking movements (chorea)
  • Muscle rigidity and contractures
  • Slow or abnormal eye movements
  • Impaired gait, posture, and balance
  • Difficulty with speech and swallowing
  • Elbow weakness and general muscle weakness

Cognitive Impairments

  • Difficulty organizing and prioritizing
  • Lack of flexibility in thinking
  • Getting stuck on thoughts or actions
  • Lack of impulse control
  • Difficulty learning new information
  • Slowed thought processing

Psychiatric Disorders

  • Depression (very common)
  • Anxiety and nervousness
  • Irritability and mood swings
  • Social withdrawal
  • Insomnia
  • Apathy and fatigue
  • Thoughts of death or suicide

Disease Progression Stages

Early Stage (0-8 years from diagnosis)

  • Subtle changes in coordination, minor involuntary movements
  • Difficulty thinking through complex problems
  • Depression and irritability
  • Still able to work and manage daily activities independently

Middle Stage (5-16 years from diagnosis)

  • More pronounced movement problems
  • Diminished ability to work or manage household
  • Difficulty with speech and swallowing
  • May need assistance with daily activities
  • Thinking and reasoning more impaired

Late Stage (11-26 years from diagnosis)

  • Requires full-time care
  • Unable to walk or speak
  • May not recognize family members
  • Completely dependent for all activities
  • Choking becomes a major concern

Juvenile Huntington's Disease

When symptoms begin before age 20, it's called juvenile HD. This form progresses more rapidly and may present differently:

  • Behavioral problems and learning difficulties
  • Rapid decline in school performance
  • Seizures (30-50% of children with juvenile HD)
  • Stiffness rather than chorea
  • Typically inherited from the father

Causes

Huntington's disease is caused by a hereditary defect in a single gene. It's an autosomal dominant disorder, meaning only one copy of the defective gene is needed to develop the disease.

Genetic Mechanism

How the Mutation Causes Disease

Inheritance Pattern

Risk Factors

The primary risk factor for Huntington's disease is having a parent with the condition. Other factors influence disease presentation and progression:

Genetic Risk Factors

Factors Affecting Disease Progression

Predictive Testing Considerations

Diagnosis

Diagnosing Huntington's disease involves clinical assessment, family history, and genetic testing. Early diagnosis can be challenging as initial symptoms may be subtle and vary among individuals.

Clinical Evaluation

Genetic Testing

Imaging Studies

Differential Diagnosis

Conditions that may mimic HD include:

Treatment

While there is no cure for Huntington's disease, treatments can help manage symptoms and improve quality of life. A multidisciplinary approach involving various specialists provides the best care.

Medications for Movement Symptoms

Medications for Psychiatric Symptoms

Therapies and Support

Experimental Treatments

Comprehensive Care Team

HD management requires a multidisciplinary team including:

  • Neurologist specializing in movement disorders
  • Psychiatrist
  • Genetic counselor
  • Physical, occupational, and speech therapists
  • Social worker
  • Nutritionist
  • Palliative care specialist

Living with Huntington's Disease

Managing HD requires adapting to progressive changes while maintaining quality of life. Support for both patients and families is crucial throughout the disease course.

Daily Living Strategies

Planning Ahead

Support Resources

When to See a Doctor

Early medical intervention can help manage symptoms and improve quality of life. Seek medical attention for:

If You're At Risk

For Diagnosed Individuals

Emergency Situations

Related Conditions

Several conditions share features with or may be confused with Huntington's disease:

Frequently Asked Questions

Should I get tested if my parent has Huntington's disease?

This is a deeply personal decision with no right or wrong answer. Predictive testing can confirm whether you carry the HD gene mutation, but it cannot tell you when symptoms will start or how severe they will be. Consider genetic counseling to explore the implications for you and your family. Some people want to know for family planning or life decisions, while others prefer not to know. Testing is generally not recommended for children under 18 unless they show symptoms.

Can lifestyle changes slow the progression of HD?

While lifestyle changes cannot stop HD progression, they may help maintain function and quality of life longer. Regular physical exercise appears to have neuroprotective effects and can help with mood and motor symptoms. Mental stimulation through puzzles, reading, or social activities may help preserve cognitive function. A healthy diet, adequate sleep, and stress management are also beneficial. Some studies suggest that people who remain active physically and mentally may have a slower functional decline.

What's the difference between adult-onset and juvenile HD?

Juvenile HD occurs when symptoms begin before age 20 and accounts for about 5-10% of cases. It often presents differently than adult-onset HD, with more rigidity and dystonia rather than chorea, rapid cognitive decline, seizures in 30-50% of cases, and behavioral problems. Juvenile HD typically progresses faster than adult-onset disease. It's usually inherited from the father due to genetic anticipation, where CAG repeats expand during sperm production. Children with juvenile HD often have more than 60 CAG repeats.

How do I talk to my children about HD in the family?

Be honest but age-appropriate. Young children need to know that someone is sick but don't need genetic details. Teenagers can understand more about inheritance and may have questions about their own risk. Emphasize that HD is not contagious and nothing they did caused it. Provide reassurance and support, and consider family counseling. Let them know testing is available when they're adults if they choose. The Huntington's Disease Youth Organization (HDYO) offers excellent resources for young people.

What research gives hope for future treatments?

Several promising approaches are in development. Gene silencing therapies using antisense oligonucleotides (ASOs) or RNA interference aim to reduce production of the toxic huntingtin protein. Early trials have shown the ability to lower mutant huntingtin levels. Gene editing technologies like CRISPR may eventually correct the mutation. Cell replacement therapies using stem cells could replace damaged neurons. Small molecule drugs targeting various aspects of HD pathology are in trials. While a cure isn't imminent, these approaches offer real hope for disease-modifying treatments.

References

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  8. Huntington's Disease Society of America. Family Guide Series. 2021.