Huntington Disease (HD)

Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded cytosine-adenine-guanine (CAG) repeat in the huntingtin gene. This mutation results in extra polyglutamine (PolyQ) repeats in the huntingtin protein, which causes it to misfold and accumulate in neurons. Aggregates of the mutated huntingtin protein impair normal nerve cell function and eventually lead to neuronal death.^1,2

HD is characterized by progressive neuropsychiatric symptoms, behavioral anomalies, neurocognitive impairments, and motor dysfunction, such as chorea, bradykinesia, dystonia, muscle rigidity, impaired communication, and swallowing problems. As the disease advances, symptoms (such as dystonia and difficulty swallowing) gradually progress to complications such as pneumonia, cardiac disease, and infections, which may lead to early death. Comprehensive medical and supportive care may help effectively manage complications in patients with HD.^1,2

Progressive Motor Impairments

As HD advances, severe large-amplitude chorea, bradykinesia, and dystonia can lead to loss of mobility, poor positioning, falls, injuries, fractures, and head trauma. Patients may develop pressure sores on the body due to lack of mobility.¹ 

Read more about HD clinical features

Respiratory Complications

Weakened swallowing reflexes, worsening dystonia, impaired mobility, reduced physical activity and exercise capacity, reduced muscle control, decreased respiratory muscle strength, and compromised lung function can increase the risk of respiratory infections, especially pneumonia.³ Aspiration pneumonia has been reported as a common cause of death in patients with HD.⁴ These infections can lead to serious complications and contribute to an overall decline in health. Patients may also experience sleep-related breathing disorders, such as sleep apnea, due to effects on muscle tone and muscle control during sleep in the late stages of the disease.⁵

Cardiac Complications

Patients with HD may experience cardiac problems, such as coronary heart disease, decreased vagal modulation of the heart rate, conduction abnormalities related to cardiac electrical remodeling, QT interval alterations, and atrial and ventricular fibrillation. These may lead to further cardiovascular complications such as cardiac arrhythmias, syncope, and sudden cardiac death. The second most common cause of mortality among patients with HD is cardiovascular disease leading to heart failure, which accounts for 20% to 30% of deaths.⁶

Read more about HD prognosis

Worsening Dysphagia

As HD progresses, dysphagia worsens, leading to an increased likelihood of food, liquids, or medications entering the airway, which can cause repeated aspiration and choking. This can lead to respiratory distress and infections such as pneumonia.⁷

Nutritional Complications

In addition to swallowing and eating difficulties due to dysphagia, patients may lose interest in eating, resulting in vitamin and mineral deficiencies, malnutrition, dehydration, obstipation, and weight loss. This may result in an overall decline in health, decreasing the body’s immunity and ability to heal.^2,7

Read more about HD diet and nutrition

Infections

Infections, such as pneumonia, skin infections, and urinary tract infections, can develop as a result of overall health deterioration.⁷

Loss of Communication

Progressive dysarthria can eventually lead to complete loss of verbal communication. This may result in patients communicating nonverbally through facial expressions, gestures, or communication boards.⁸

Read more about HD treatment

Progressive Cognitive Decline

In the advanced stage of HD, neurocognitive functions continue to deteriorate, with profound impairments in memory and information processing. This can lead to symptoms such as disorientation to time and space, disinhibition, perseveration, inflexible thinking, and severe bradyphrenia. Patients may also lose the ability to recognize family members.²

Worsening Behavioral Symptoms

In the advanced stage of HD, psychiatric symptoms such as depression, anxiety, agitation, aggression, and mood swings may worsen, with patients screaming or crying without reason. While some patients may experience increasing irritability that can escalate to violent behavior, other patients may become increasingly apathetic or impulsive. These behavioral issues are distressing to the patient, their family, and caregivers.²

Read more about HD therapies

Chronic Pain

Chronic pain is more common in the later stage of HD. It may be caused by hypokinesis, dystonia, spasticity or hyperkinetic movements, and injury.²

Bedridden State

Severe motor impairments, physical dependence, and progressive cognitive decline may result in a complete loss of autonomy in patients who become confined to a bed or wheelchair.²

Impact on Caregivers

In the advanced stage of HD, caregivers may feel burdened, as patients become almost entirely dependent on them for daily activities, such as eating, drinking, taking a bath, or going to the toilet.²

References

1. Ajitkumar A, De Jesus O. Huntington disease. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. Updated February 12, 2023. Accessed August 14, 2023. 
2. Boersema-Wijma DJ, van Duijn E, Heemskerk AW, van der Steen JT, Achterberg WP. Palliative care in advanced Huntington’s disease: a scoping review. BMC Palliat Care. 2023;22(1):54. doi:10.1186/s12904-023-01171-y
3. van de Zande NA, Massey TH, McLauchlan D, et al. Clinical characterization of dystonia in adult patients with Huntington’s disease. Eur J Neurol. 2017;24(9):1140-1147. doi:10.1111/ene.13349
4. Heemskerk AW, Roos RAC. Aspiration pneumonia and death in Huntington’s disease. PLoS Curr. 2012;4:RRN1293. doi:10.1371/currents.RRN1293
5. Jones U, Busse M, Enright S, Rosser AE. Respiratory decline is integral to disease progression in Huntington’s disease. Eur Respir J. 2016;48(2):585-588. doi:10.1183/13993003.02215-2015
6. Rossi M, Wainsztein N, Merello M. Cardiac involvement in movement disorders. Mov Disord Clin Pract. 2021;8(5):651-668. doi:10.1002/mdc3.13188
7. End-of-life care in Huntington disease. Huntington Society of Canada. July 2016. Accessed August 14, 2023.
8. Speech. Huntington’s Disease Society of America. Accessed August 14, 2023.

Reviewed by Kyle Habet, MD, on 8/22/2023.

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Erum Naqvi, PhD

Erum Naqvi obtained her Ph.D. in Molecular Medicine from Hannover Medical School (Germany) after completing her Masters in Biomedical Science and Bachelors in Microbiology from University of Delhi (India). She has several years of experience as a science writer.