Huntington's Disease Flashcards
Definition
Autosomal dominant trinucleotide repeat disease characterised by progressive chorea and dementia, typically commencing in middle age
Aetiology
- The huntingtin gene codes for a protein called huntingtin
- In the huntingtin gene there is a trinucleotide repeat expansion (CAG) that results in toxic gain of function
- Autosomal DOMINANT
- Earlier age of onset with each successive generation
Epidemiology
• Average age of onset: 30-50 yrs
Presenting symptoms
- Family history
- INSIDIOUS onset in middle-age
- Progressive
- Fidgeting
- Clumsiness
- Involuntary, jerky, dyskinetic movements often accompanied by grunting and dysarthria
• Enquire about drug history (especially cocaine and anti-psychotics)
Presenting symptoms (early cognitive changes)
o Lability o Dysphoria (a state of unease or generalised dissatisfaction with life) o Mental inflexibility o Anxiety o Develops into dementia
Presenting symptoms (late stages)
o Rigid
o Akinetic
o Bed-bound
Signs on physical examination
- Chorea
- Dysarthria
- Slow voluntary saccades
- Supranuclear gaze restriction
- Parkinsonism
- Dystonia
- MMSE shows cognitive and emotional deficits
Investigations
• Genetic Analysis
o Diagnostic if there are > 39 CAG repeats in the HD gene
o Reduced penetrance leads to an intermediate number of CAG repeats
• Imaging
o Brain MRI or CT may show symmetrical atrophy of the striatum and butterfly dilation of the lateral ventricles
• Bloods
o To exclude other pathology