Huntington's Disease

Definition

Huntington's Disease (HD) is a progressive, inherited neurodegenerative disorder characterised by motor dysfunction, cognitive decline, and psychiatric symptoms. It is caused by a genetic mutation leading to the gradual degeneration of neurons in specific areas of the brain, particularly the basal ganglia and cerebral cortex.

Aetiology

Huntington's Disease is caused by an autosomal dominant mutation in the HTT gene, which encodes the huntingtin protein. This mutation involves an abnormal expansion of CAG repeats in the gene:

Normal: <40 CAG repeats
Intermediate: 27-35 CAG repeats (may not cause HD but can expand in offspring)
Mutant: >40 CAG repeats (causes HD, with earlier onset associated with higher repeat numbers)

Pathophysiology

The abnormal huntingtin protein resulting from the HTT gene mutation accumulates within neurons, leading to cellular dysfunction and death. The basal ganglia, particularly the striatum, are heavily affected, resulting in the characteristic motor symptoms of HD. Additionally, the degeneration of cortical neurons contributes to cognitive and psychiatric symptoms.

Risk Factors

Family history: Having a parent with Huntington's Disease significantly increases the risk of inheriting the condition.
Genetic predisposition: Carrying the mutant HTT gene with expanded CAG repeats.

Signs and Symptoms

Chorea: Involuntary, jerky movements of the limbs, face, and trunk.
Bradykinesia: Slowness of movement.
Dystonia: Sustained muscle contractions causing abnormal postures.
Cognitive decline: Memory loss, difficulty with concentration, and executive dysfunction.
Psychiatric symptoms: Depression, irritability, anxiety, and obsessive-compulsive behaviours.
Difficulty with speech and swallowing.

Investigations

Clinical history and physical examination, focusing on neurological and psychiatric assessment.
Genetic testing to identify the HTT gene mutation.
Neuroimaging: MRI or CT scan to assess brain atrophy, particularly in the basal ganglia.
Neuropsychological testing to evaluate cognitive function.

Management

Primary Care Management

Initial assessment and referral to a neurologist or genetic specialist for further evaluation and diagnosis.
Supportive care, including managing symptoms and providing information and support to patients and families.
Coordination of multidisciplinary care, involving physiotherapists, occupational therapists, speech therapists, and dietitians.

Specialist Management

Medications to manage motor symptoms: Tetrabenazine and deutetrabenazine for chorea.
Antidepressants and antipsychotics for psychiatric symptoms.
Speech therapy for communication difficulties and swallowing issues.
Physiotherapy to maintain mobility and prevent contractures.
Occupational therapy to assist with daily activities and adaptive equipment.
Genetic counselling for families.

Example Management for Huntington's Disease

A patient presenting with symptoms of Huntington's Disease should be referred to a neurologist for a comprehensive evaluation, including genetic testing to confirm the diagnosis. If diagnosed, the patient may be prescribed tetrabenazine to manage chorea and antidepressants for psychiatric symptoms. A multidisciplinary team approach involving physiotherapy, occupational therapy, and speech therapy is essential to support the patient's needs. Regular follow-up is necessary to monitor disease progression and adjust the care plan as needed.

References

NICE. (2024). Huntington's Disease: Management. Retrieved from NICE
NHS. (2023). Huntington's Disease. Retrieved from NHS
Walker, F. O. (2007). Huntington's Disease. The Lancet.
Roos, R. A. C. (2010). Huntington's Disease: A Clinical Review. Orphanet Journal of Rare Diseases.
Reiner, A., et al. (2011). Huntington's Disease: From the Patient to the Laboratory and Back Again. Springer.