Huntington's Disease

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Huntington’s disease (HD) is a progressive, inherited neurodegenerative disorder characterised by involuntary movements (chorea), cognitive decline, and psychiatric disturbances.

Aetiology

Huntington’s disease is caused by a genetic mutation in the HTT gene, which encodes the huntingtin protein.

• Autosomal dominant inheritance: a child of an affected parent has a 50% chance of inheriting the condition.
• Trinucleotide repeat expansion: an increased number of CAG repeats (>40) in the HTT gene leads to disease development.
• Anticipation: the disease may present at an earlier age in successive generations due to increasing CAG repeat length.

Pathophysiology

• Abnormal huntingtin protein accumulates and leads to neuronal death.
• Primarily affects the caudate nucleus and putamen (striatum), leading to movement disorders.
• Loss of inhibitory pathways in the basal ganglia results in excessive movement (chorea).
• Progressive degeneration extends to the cortex, causing cognitive and psychiatric symptoms.

Risk factors

• Family history of Huntington’s disease.
• Parental transmission (paternal inheritance often associated with earlier onset).

Signs and symptoms

Symptoms typically appear between ages 30-50 and progress over 10-20 years.

Motor Symptoms:

• Chorea: involuntary, jerky movements of the face, limbs, and trunk.
• Dystonia: abnormal posturing due to muscle contractions.
• Bradykinesia: slowness of movement.
• Loss of coordination: difficulty with fine motor tasks and balance.
• Dysphagia: difficulty swallowing in later stages.

Cognitive Symptoms:

• Executive dysfunction (poor planning, decision-making).
• Memory loss and difficulty concentrating.
• Impaired judgement and reduced mental flexibility.

Psychiatric Symptoms:

• Depression: common and may precede motor symptoms.
• Anxiety and irritability.
• Psychosis: hallucinations, delusions in advanced disease.
• Personality changes: social withdrawal, impulsivity.

Investigations

• Genetic testing: confirms diagnosis by detecting expanded CAG repeats in the HTT gene.
• MRI brain: shows caudate nucleus atrophy and widened lateral ventricles.
• Neuropsychological assessment: evaluates cognitive function.
• Functional assessments: helps track disease progression.

Management (under specialist treatment)

1. Symptomatic Treatment:

For Chorea (Involuntary Movements):

• Tetrabenazine: reduces dopamine activity, helping with chorea.
• Antipsychotics (e.g., risperidone, olanzapine): may help suppress movement disorders and psychiatric symptoms.

For Psychiatric Symptoms:

• SSRIs (e.g., sertraline, fluoxetine): for depression and anxiety.
• Atypical antipsychotics: for psychosis or severe agitation.

2. Supportive Care:

• Physiotherapy to maintain mobility and prevent falls.
• Occupational therapy for adaptive aids.
• Speech therapy for communication and swallowing difficulties.
• Dietary support due to weight loss from swallowing difficulties.

3. Genetic Counselling:

• Offered to at risk family members considering predictive genetic testing.

4. Palliative Care:

• Focuses on symptom relief in advanced stages.
• End of life planning and support for carers.