Autosomal dominant.
HTT gene of Chromosome 4p16.3, coding for huntingtin.
Trinucleotide repeat disease of poly–glutamine. [CAG]
Neurodegenerative disease.
Expansion of trinucleotide starts from spermatogenesis of father -> Early onset in child.
Clinical features
- 30s – 40s. Onset and severity depends on HTT gene repeat amount.
- Progressive movement disorder (Motor – 1st)
- Chorea – Jerky hyperkinetic dystonic movement of whole body
- Choreo-athetosis
- Dementia (Cognitive – 2nd)
- Death due to pneumonia and suicide (no cure).
Morphology
Intranuclear huntingtin inclusions. (neuroprotective mechanism of the neuron).
Stained with IHC for Ubiquitin.
Affects Striatum and Cortex neurons nearer to the ventricle. (tail of caudate nucleus)
Small brain. Atrophy of Caudate and Putamen.
Dilated lateral and third ventricles.
Affected neurons:
Medium sized spiny neurons containing these neurotransmitters:
GABA, enkephalin, dynorphin, substance-P.