Huntington's Disease

Front 1

What is the inheritance pattern for Huntington's Disease?

Back 1

autosomal dominant with anticipation

Front 2

HD is due to an expansion of the ________ gene on chromosome ____.

Back 2

huntington; 4

Front 3

T/F: HD demonstrates a low degree of penetrance

Back 3

False

Front 4

Signs/Symptoms of HD

Back 4

chorea (cardinal manifestation)
behavioral and personality disorders
dystonia
dysarthria
dementia

Front 5

HD has been hypothesized to result from a ___ of function mutation.

Back 5

gain

Front 6

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 __.

Back 6

80; 45

Front 7

What are the symptoms of Juvenile HD?

Back 7

rigidity, tremor, dystonia, myoclonic epilepsy, dementia

Front 8

HD patients have an expanded _ _ _ allele.

Back 8

CAG

Front 9

An individual with __ or more repeats will likely develop HD sometime in their life.

Back 9

40

Front 10

Someone with fewer than __ repeats will not likely develop HD.

Back 10

36

Front 11

What are some non-translated trinucleotide repeat disorders?

Back 11

Fragile X & Myotonic dystrophy

Front 12

What are some translated trinucleotide repeat disorders?

Back 12

Spinobulbar muscular atrophy (Kennedy syndrome)
Spinocerebellar ataxia (type 1 & 7)
HD
Dentatorubropallidoluysian atrophy (DRPLA)
Machado-Joseph

Front 13

Expanision of repeats in HD occurs in ___________ transmission.

Back 13

Paternal

Front 14

What area of the brain is most affected by HD?

Back 14

caudate

Front 15

What part of the brain (specifically) is affected earliest in HD?

Back 15

the tail of the caudate

Front 16

What kind of neurons are lost in the caudate and putamen in HD?

Back 16

medium spiny neurons

Front 17

In what order are the types of medium spiny neurons lost in HD?

Back 17

1st: enkephalinergic neurons
2nd: Substance P neurons (lost only later in disease)

Front 18

The striatum excites the globus pallidus via which pathway?

Back 18

indirect (direct inhibits)

Front 19

The enkephalinergic neurons in the striatum project to the globus pallidus via the direct or indirect pathway?

Back 19

indirect

Front 20

What is the simplified pathway of basal ganglia circuitry involved HD?

Back 20

cerebral cortex excites striatum -->
striatum inhibits medial globus pallidus (via direct or indirect pathway) -->
project to thalamus -->
projects back to cortex

Front 21

Is the pathway from the cortex to the basal ganglia excitatory or inhibitory?

Back 21

excitatory

Front 22

In HD there is a preferential loss of neurons to the _________.

Back 22

lateral globus pallidus

Front 23

T/F: In Juvenile HD there is a preferential loss of neurons to the medial globus pallidus.

Back 23

False: in Juvenile HD there is equal loss to lateral and medial globus pallidus

Front 24

What are two hypotheses about HD pathophysiology?

Back 24

1. excitatory amino acids are involved
2. mitochondrial energy metabolism may contribute to nerve degeneration

Front 25

In what tissue is the protein that the huntington gene encodes found?

Back 25

all tissue

Front 26

Where in the cell is the protein encoded by the huntington gene found?

Back 26

cytoplasm

Front 27

Do HD brains show an increase or decrease in the huntington protein?

Back 27

decrease

Front 28

What are some potential therapies for HD (demonstrated in mouse models)?

Back 28

creatine
ciliary neurotrophic factor
environmental enrichment

Front 29

How many CAG repeats does a normal person have?

Back 29

less than 26

Front 30

What are some current treatment options for chorea?

Back 30

Benign neglect is best
neuroleptics
occupational and physical therapy
speech therapy
medications (atypical antipsychotics, amantidine, tetrabenazine)