Huntington disease (HD) is a neurodegenerative movement disorder characterized by involuntary and irregular movements of the limbs, neck, head, and/or face (chorea). This autosomal-dominant inherited disease is caused by mutations (increased number of CAG trinucleotide repeats) in the huntingtin gene which eventually leads to the dysfunction of subcortical motor circuits. Symptom onset depends on the individual extent of the genetic abnormalities but usually occurs around 40 years of age. In later stages, psychiatric symptoms like dementia and depression are common. To date, no disease-modifying treatment is available. Management involves symptomatic treatment and supportive care. On average, HD leads to death within 15–20 years after symptom onset.
- Sex: ♂ = ♀
Peak incidence 
- ∼ 40 years of age (symptom onset usually between 20 and 50 years of age)
- One of the most common hereditary diseases of the brain
Epidemiological data refers to the US, unless otherwise specified.
Increased number of CAG repeats (trinucleotide or triplet repeat expansion) in the huntingtin gene on chromosome 4 (most likely due to DNA polymerase dysfunction) results in the expression of an altered huntingtin protein.
- Huntingtin is physiologically expressed throughout the CNS, but its exact function is not known.
- 40 or more CAG repeats result in almost certain development of HD .
- Inheritance 
- Overall levels of abnormal huntingtin protein correlate with the severity of symptoms.
The striatum normally controls movement via inhibitory outputs to the globus pallidus internus (direct pathway) and globus pallidus externus (indirect pathway). 
- Direct pathway
- Striatal projections inhibit the external globus pallidus, which normally inhibits the subthalamic nucleus.
- The subthalamic nucleus possesses excitatory projections to the internal globus pallidus which in turn projects to the thalamus and ultimately to the cortex.
- Activation of the indirect pathway generally results in decreased transmission to the cortex.
- In HD, the indirect pathway is commonly affected earlier than the direct pathway. 
- Early stages: only the indirect pathway is affected → increased dopaminergic transmission → excess cortical activity → hyperkinetic/choreatic movements 
- Later stages: both pathways are affected: , which, together with additional factors → overall decrease of excitatory thalamic transmission to the cortex → hypokinetic/akinetic symptoms
- Neuronal injury and death is caused by overactivation of N-methyl-D-aspartate (NMDA) receptors through excessive glutamate stimulation (glutamate-induced excitotoxicity), which leads to:
In Huntington disease, increased number of CAG repeats leads to the damage to the Caudate nucleus and results in decreased Ach and GABA.
- Movement dysfunction 
- Sensory deficits
- Autonomic symptoms: hyperhidrosis, urinary incontinence
Advanced stages 
- Movement dysfunction
- Cognitive decline and behavioral changes (these symptoms may mimic substance use) 
- Cachexia (due to dysphagia and high energy consumption)
- Atypical symptoms
- Patient history
- Genetic testing (e.g. polymerase chain reaction)
- Imaging: rarely used 
Differential diagnosis of choreoathetoid movement disorders
|Epidemiology & etiology||Signs & symptoms||Diagnostics|
Huntington disease 
| || |
|Ballismus || |
Drug-induced chorea 
| || |
The differential diagnoses listed here are not exhaustive.
- Ongoing physiotherapeutic, ergotherapeutic, and logotherapeutic care
- Psychotherapy (if needed)
- Consultation of specially trained counselors (if genetic diagnostics are employed)
Medical therapy 
- Hyperkinetic/choreatic movements
- Psychosis: atypical neuroleptics (e.g., clozapine)
- Depression: SSRIs (e.g., citalopram)
There is no causal therapy available.