Introduction

Huntington’s disease – HD – (aka Huntington’s chorea, named after George Huntington [1872]) is an autosomal dominant disorder that shows full penetrance.
  • Treatment is supportive only

Epidemiology and Aeitiology

Approximately affects 5-10 per 100 000 individuals

  • Incidence highest in those of western European descent, and lowest in Black Africans

Men and women affected equally

Genetics & Pathology

Sufferers carry a defect in chromosome 4 on the Huntgingtin gene (HTT). The normal Huntingtin gene codes for the amino acid glutamine. The gene contains a trinucleotide repeat sequence (CAG). In normal individuals, the repeat is not problematic. As the repeat becomes longer, it may reach a threshold. Once the repeat has surpassed the threshold, then Huntington’s disease results.

  • At 36-40 repeats, the disease exists with reduced penetrance
  • At >40 repeats, the disease exists with full penetrance
  • Some sufferers may have hundreds of repeats. In such severe disease, onset may be before the age of 20 (7% of cases), and may be referred to as juvenile HD

The length of this repeat sequence determines the onset and severity of the disease. The longer the repeat, the greater the severity and earlier the onset
The repeat can lengthen with subsequent generations leading to a worse phenotype over time, within the same family.
The protein produced by the defective HTT gene causes increased neuronal damage via unknown mechanisms.
 Genetic testing is available to asses if an individual is affected. Patients will also usually receive genetic counselling. As symptoms don’t typically present until after child bearing age, families may already have children and grandchildren who may/may not wanted to be tested – if 1 parent is affected, there is a 50% risk of an affected child
Pathology

  • There is cerebral and caudate nucleus/corpus striatum atrophy due to the loss of GABA-nergic and cholinergic neurons. – the caudate nucleus is located within the corpus striatum. The corpus striatum is located just beneath the lateral ventricles, either side of the thalamus, and divided into the caudate nucleus (which projects into the ventricle) and the lenticular nucleus, external to the ventricles).
  • Imaging (MRI / CT) is often performed to rule out alternative diagnosis. HD will show squaring off of the ventricle edges – boxcar ventricles where the caudate nucleus has atrophied.

Presentation

Age of onset typically 35-50
Initially symptoms may be sporadic, but then become progressive, typically in the order:

  • Chorea Agitation Dementia ± seizures Death
  • Symptoms may also present simultaneously
  • Antisocial behaviour disorders (including bi-polar and schizophtrenia) may also exist
  • Motor signs  – Chroea – these typically include involuntary short sharp muscle movements, gait problems, grimacing, dystonia and motor impersistence whereby muscle contractions cannot be sustained (e.g. as demonstrated by protrusion of the tongue)
  • Progression – ultimately, patients will have difficulty walking and swallowing and will suffer from severe dementia.

Treatment

Is typically only supportive
Antipsychotics (e.g. chlorpromazine, haloperidol) can be useful o reduce chorea and agitation, but do not later disease progression. They are usually titrated up to the maximum tolerable dose.

  • GABA affecting treatments have been proven ineffective. Experimental therapies are looking at NMDA receptors and enhancing mitochondrial energy production.

Counseling to both patient and family, and the offer of genetic testing are important.

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