Huntingtons Flashcards
what is the age of onset of Huntington’s Disease?
35-50
what is the the correlation between repeat length and penetrance in Huntingtons?
Repeat length may reach a threshold. Once surpassed Huntington’s disease results.
o 36-40 - reduced penetrance
o At >40- disease exists with full penetrance
what is the hereditary pattern of Huntington’s?
Autosomal dominant
what is the cause of Huntington’s?
expanded CAG repeat at the N terminus of chromosome 4p16.3
what is the mechanism of Huntington’s?
CAG repeat generates an elongated polyglutamine tail on the huntington protein, which leads to cleavage and the generation of toxic fragments of this abnormal protein
what is the cellular consequence of Huntington protein fragments?
proteins interfere with energy production, regulation of transcription, axonal and vesicular transport, apoptosis, proteasome function, and cell-cell interactions
which part of the brain does Huntingtons affect?
striatum - chorea
what is the consequence of huntingtons in the chorea?
o neuronal loss in projections to other basal ganglia structures.
o cells of the deep layers of the frontal and parietal cortex are lost (corticostriatal projections)
what is the neurochemical basis of huntingtons?
deficiency of GABA and acetylcholine with reduced activity of enzymes glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT).
what is the disease progression of huntingtons?
Chorea ≫ Agitation ≫ Dementia ± seizures ≫ Death
what is the triad of symptoms associated with Huntington’s?
Chorea
Rigidity
Dementia
what are the features chorea?
Random movements of fingers and toes, with occasional peculiar postures of hands, trunk, or limbs, and odd facial expressions
what are the features of dementia in Huntington’s disease?
subcortical, early onset (30-50), dysexecutive syndrome and slowed speed of processing. Eventual involvement of memory, Associated changes in mood, personality and later psychosis
what are the motor symptoms associated with huntingtons?
hypotonicity, primitive reflexes, twitching, loss of coordination, slow eye movements, loss of fine motor skills, choreiform movements, writhing movements, gait disturbance, rigidity, problems chewing/swallowing/speaking
what are the psychiatric symptoms of huntingtons?
depression, compulsions, suicidality, aggression, blunted affect, psychosis, anxiety
