Genetic Conditions Flashcards
What is the definition of Huntington’s Disease?
HD, also known as Huntington’s chorea is an inherited disorder that results in death of brain cells. It affects 4 to 8 per 100,000. It is caused by an expanded CAG repeat at the N-terminus of the gene that codes for the huntingtin protein
What is the aetiology of Huntington’s disease?
HD is typically inherited from a person’s parents by an autosomal dominant mutation. However, 10% are due to a new mutation.
CAG repeats are added on by DNA polymerase. Therefore a child has more CAG repeats than their parent, as more CAG repeats are added during development, adding on to the number of repeats from their parent.
The greater the number of CAG repeats, the earlier the onset of symptoms. Therefore there is earlier onset of symptoms with each generation. This effect is called anticipation.
What are the clinical features of Huntington’s Disease?
Although movement problems are well known, psychological issues are common. This often presents as impaired workor school performance. Personality changes manifest in different ways. Irritability and temper outburst are common. Cognitive decline is often most noticeable when comparing patients to siblings.
Patients present with chorea (jerky involuntary movements) in the early stages of the disease. There may also be twitching or restlessness with patients which patients may be unaware of, or may explain them away as nervousness. Motor impersistence is the inability to maintain postures of positions.
Loss of coordination may manifest as dropping things, stumbling or motor vehicle accidents. There is also deficit in fine motor coordination. The lack of coordination and chorea, can be noted as impaired tandem walking.
On testing of eye movements, there are slowed saccades.
In advanced stages patients present with hypokinetic motor symptoms as the direct pathway is also affected as well as the indirect pathway, leading to dystonia, rigidity, and bradykinesia.
Describe the diagnosis of Huntington’s disease
A CAG repeat testing produces a positive result if there are more than 40 CAG repeats on one of the two alleles. An intermediate result is 36-39 repeats. A normal result is <36 repeats.
An MRI or CT scan may show caudate or striatal atrophy.
Describe the management of Huntington’s Disease
General management includes: ongoing physiotherapy and psychotherapy if needed.
In terms of medical therapy:
- To treat hyperkinetic/choreatic movements:
- Monoamine-depleting drugs such as tetrabenazine
- Atypical antipsychotics such as clozapine
- NMDA-receptor antagonists such as amantadine
- Atypical antipsychotics are also used to treat psychosis
- SSRIs such as citalopram are used to treat depression.
