Huntington's Disease

Question 1

What are the genetics of HD?

Answer 1

Autosomal dominant
Chromosome 4 HTT (Huntingtin gene)
Expanded trinucleotide CAG repeat (generally 40+)

Question 2

What is the pathology of HD?

Answer 2

Huntingtin protein present throughout body but primarily in CNS
Causes atrophy of caudate and putamen

Question 3

What are the three main categories of symptoms of HD?

Answer 3

1. Neurologic: chorea, dystonia, slowed eye movement, hyperreflexia, gait abnormality, myoclonus, Parkinsonism (late)
2. Cognitive: poor judgement, inflexible, lack insight, concentration, STM loss
3. Psychiatric: depression, anxiety, irritable, apathy, delusions, paranoia, disinhibition

Question 4

What is the age of onset and # of repeats in HD?

Answer 4

Onset usually in 40s (depends on number of repeats)
<26 = normal
27-35 = intermediate
36-39 = reduced penetrance (maybe affected)
40+ = full penetrance (will be affected)

Question 5

What are the three phases of HD?

Answer 5

1. Healthy phase
2. Prediagnostic phase - subtle changes in personality, cognition and motor control
3. Diagnostic phase - full presence of symptoms

Question 6

What are the diagnostic criteria for HD?

Answer 6

1. Typical clinical features: motor changes with or without psychiatric or cognitive changes
2. Family history
3. Genetic confirmation

Question 7

What does imaging show in HD?

Answer 7

Caudate atrophy

Question 7

How do you treat CI in HD?

Answer 7

No role for pharmacotherapy
Supportive management
OT assistance
SLP for communication

Question 8

How do you treat chorea in HD?

Answer 8

If causing distress or discomfort
Tetrabenazine - blocks presynaptic dopamine release, CI if uncontrolled depression or SI
Neuroleptics - dopamine receptor blocking, ex. Tiapride, sulpiride, olanzapine, risperidone, aripiprazole

Question 9

How do you treat myoclonus in HD?

Answer 9

Rare presentation
Tx if affecting QOL
Valproate
Clonazepam
Keppra

Question 10

How do you treat psychiatric disorders in HD?

Answer 10

Non pharm, ID triggers
Assess suicide risk
Agitation/aggression - SSRI
Hallucinations - antipsychotics
Sexuality - SSRI or antipsychotics

Question 11

How much does your risk for dementia increase if a first degree relative has it?

Answer 11

2x the risk
10% to 20%

Question 12

What is the risk of developing dementia if you have an autosomal dominant family hx?

Answer 12

95% lifetime risk
Myoclonus in early stages

Question 13

What percent of AD cases are due to autosomal dominant?

Answer 13

<1%

Question 14

What genes are involved in early onset AD?

Answer 14

APP (breaks down to form amyloid beta)
Presenilin 1 (inc amyloid beta production)
Presenilin 2

Question 15

What genes are involved in late onset Alzheimer’s?

Answer 15

APOE3 = wild type
APOE4 = contributor
1 allele = 2-3x risk (75% disease free)
2 alleles = 8-12x risk
APOE2 = protective 0.5x risk

Question 16

What genes are involved in autosomal dominant FTD?

Answer 16

MAPT (microtubule associated protein tau)
GRN (progranulin)
C9orf72