What is Huntington's disease?

From the Guidelines

Huntington's disease is a neurodegenerative disorder characterized by choreic movements, cognitive decline, and psychiatric changes, affecting approximately 3-5 out of 100,000 individuals, with no effective treatment available. The disease is caused by a mutation in the HTT gene, leading to the production of an abnormal protein called huntingtin, which damages brain cells over time 1.

Key Characteristics of Huntington's Disease

• Neurodegenerative disease of mid-life onset
• Produces choreic movements and cognitive decline
• Often accompanied by psychiatric changes
• Affects ~3–5 out of 100,000 individuals, with higher prevalence in some populations of western European origin 1
• Juvenile-onset HD occurs in approximately 5% of affected patients, presenting with rigidity, spasticity, and intellectual decline before the age of 20 years 1

Symptoms and Management

• Symptoms result from the selective loss of neurons, most notably in the caudate nucleus and putamen
• Currently, there is no effective treatment, but medications can help manage symptoms
• Tetrabenazine and deutetrabenazine are FDA-approved to control chorea, while antipsychotics, antidepressants, and mood stabilizers may address psychiatric symptoms [no specific citation available, but based on general medical knowledge]
• Physical therapy, occupational therapy, and speech therapy are important supportive treatments

Inheritance and Genetic Testing

• The disease is inherited in an autosomal dominant pattern, meaning children of affected parents have a 50% chance of inheriting the condition
• Genetic testing can confirm diagnosis and is available for at-risk individuals, though this decision requires careful consideration with genetic counseling 1

From the Research

Definition and Characteristics of Huntington's Disease

• Huntington's disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances, and dementia 2.
• It is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene 2, 3.
• The longer the CAG repeat, the earlier the onset of disease, with symptoms starting before the age of 20 years in some cases, known as Juvenile Huntington's disease (JHD) 2.

Clinical Features and Diagnosis

• The classic sign of HD is chorea that gradually spreads to all muscles, with all psychomotor processes becoming severely retarded 2.
• Patients experience psychiatric symptoms and cognitive decline, with diagnosis based on clinical symptoms and signs in an individual with a parent with proven HD, and confirmed by DNA determination 2, 4.
• Differential diagnoses include other causes of chorea, including general internal disorders or iatrogenic disorders, as well as phenocopies (clinically diagnosed cases of HD without the genetic mutation) 2, 4.

Management and Treatment

• There is no cure for HD, with management being multidisciplinary and based on treating symptoms to improve quality of life 2, 4.
• Chorea is treated with dopamine receptor blocking or depleting agents, such as tetrabenazine, which has been shown to be effective in reducing chorea in HD patients 5.
• Antipsychotic drugs may be used to manage psychiatric symptoms, with second-generation antipsychotics preferred to reduce extrapyramidal adverse events 6.
• Supportive and symptomatic management is the mainstay of treatment, with a focus on improving quality of life and reducing symptoms 3.