Huntington's Disease 2
Terms
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copy deck
- What is the inheritance pattern for Huntington's Disease?
- autosomal dominant with anticipation
- HD is due to an expansion of the ________ gene on chromosome ____.
- huntington; 4
- T/F: HD demonstrates a low degree of penetrance
- False
- Signs/Symptoms of HD
-
chorea (cardinal manifestation)
behavioral and personality disorders
dystonia
dysarthria
dementia - HD has been hypothesized to result from a ___ of function mutation.
- gain
- All individuals who have the HD mutation will manifest the disease by the time they are ___ years old, with 50% of HD patients expressing their symptoms by age __.
- 80; 45
- What are the symptoms of Juvenile HD?
- rigidity, tremor, dystonia, myoclonic epilepsy, dementia
- HD patients have an expanded _ _ _ allele.
- CAG
- An individual with __ or more repeats will likely develop HD sometime in their life.
- 40
- Someone with fewer than __ repeats will not likely develop HD.
- 36
- What are some non-translated trinucleotide repeat disorders?
- Fragile X & Myotonic dystrophy
- What are some translated trinucleotide repeat disorders?
-
Spinobulbar muscular atrophy (Kennedy syndrome)
Spinocerebellar ataxia (type 1 & 7)
HD
Dentatorubropallidoluysian atrophy (DRPLA)
Machado-Joseph - Expanision of repeats in HD occurs in ___________ transmission.
- Paternal
- What area of the brain is most affected by HD?
- caudate
- What part of the brain (specifically) is affected earliest in HD?
- the tail of the caudate
- What kind of neurons are lost in the caudate and putamen in HD?
- medium spiny neurons
- In what order are the types of medium spiny neurons lost in HD?
-
1st: enkephalinergic neurons
2nd: Substance P neurons (lost only later in disease) - The striatum excites the globus pallidus via which pathway?
- indirect (direct inhibits)
- The enkephalinergic neurons in the striatum project to the globus pallidus via the direct or indirect pathway?
- indirect
- What is the simplified pathway of basal ganglia circuitry involved HD?
-
cerebral cortex excites striatum -->
striatum inhibits medial globus pallidus (via direct or indirect pathway) -->
project to thalamus -->
projects back to cortex - Is the pathway from the cortex to the basal ganglia excitatory or inhibitory?
- excitatory
- In HD there is a preferential loss of neurons to the _________.
- lateral globus pallidus
- T/F: In Juvenile HD there is a preferential loss of neurons to the medial globus pallidus.
- False: in Juvenile HD there is equal loss to lateral and medial globus pallidus
- What are two hypotheses about HD pathophysiology?
-
1. excitatory amino acids are involved
2. mitochondrial energy metabolism may contribute to nerve degeneration - In what tissue is the protein that the huntington gene encodes found?
- all tissue
- Where in the cell is the protein encoded by the huntington gene found?
- cytoplasm
- Do HD brains show an increase or decrease in the huntington protein?
- decrease
- What are some potential therapies for HD (demonstrated in mouse models)?
-
creatine
ciliary neurotrophic factor
environmental enrichment - How many CAG repeats does a normal person have?
- less than 26
- What are some current treatment options for chorea?
-
Benign neglect is best
neuroleptics
occupational and physical therapy
speech therapy
medications (atypical antipsychotics, amantidine, tetrabenazine)