20th July 2023

Huntington’s Disease (HD)

HD is an inherited, progressive neurodegenerative disorder, which predominantly causes chorea, impaired cognition and psychiatric conditions.

Pathophysiology

HD is inherited in an autosomal dominant manner, although 10% of cases are due to a de novo mutation. A mutation in the HTT gene located on the short arm of chromosome 4 leads to the expansion of the CAG trinucleotide segment. This leads to patchy neuronal loss in the cerebellum, occurring predominantly in the basal ganglia. HD demonstrates a phenomenon known as genetic anticipation; this means that each subsequent generation tends to experience symptoms at an earlier age.

Signs and Symptoms

Onset is usually in the 30s-/40s, and initial symptoms tend to be mood change or cognitive impairment. As the disease progresses, ataxia and poor gait follow.

It is classed as juvenile if onset is in the 20s – the predominant symptoms initially tend to be hypokinesia, then behavioural changes, including poor attention span, contractures, tremors, frequent falls, and seizures.

Table 3: Symptoms of Huntington’s Disease

Complications

Complications include aspiration pneumonia, falls and dysphagia. Clinical depression isn’t uncommon and increases the risk of suicide, which is a cause of death in 9% of patients. The rate of disease progression varies, and the prognosis tends to be 10-30 years.

Diagnosis

Clinical examination and history, common in those over 40 years.

Genetic testing for the mutant HTT gene and CAG nucleotide repeats.

Imaging such as MRI head or CT head can show atrophy of the caudate nuclei. However, this is not singularly diagnostic for HD.

Management

Currently, management is for the best supportive care. Certain medications can be used to help manage symptoms, such as tetrabenazine for chorea, and antidepressants and antiepileptics to help stabilise mood. An MDT approach including speech and language therapists, physiotherapists and occupational therapists is required.