Huntington's Disease

Question 1

What is Huntington’s disease?

Answer 1

Huntington’s disease is a slowly progressive, neurodegenerative disorder characterised by:

• chorea
• incoordination
• cognitive decline
• personality changes
• psychiatric symptoms

culminating in –>

• immobility
• mutism
• inanition (starvation)

It is an autosomal dominant, trinucleotide repeat disorder that affects men and women equally.

Question 2

What is the cause of Huntington’s?

Answer 2

• HD is typically inherited, although up to 10% of cases are due to a new mutation
• Caused by an autosomal dominant mutation a gene called huntingtin
  
  • Expansion of CAG triplet repeats –> toxic gain of function
• Earlier age of onset w each successive generation

Question 3

What are the risk factors for Huntington’s?

Answer 3

• expansion of CAG repeat length at N-terminal of huntingtin gene
• family history

Question 4

Summarise the epidemiology of Huntington’s

Answer 4

• prevalence of Huntington’s in Europe’s pop. = at 4-8/ 100,000
• men = women
• 10x more common in Europeans than in those of Africans or Asians

Question 5

What is the duration of Huntington’s disease?

Answer 5

approx. 20 years from time of diagnosis (then death)

Question 6

At what age is Huntington’s typically diagnosed/ does the disease commence?

Answer 6

35 - 45 yrs (middle age)

Question 7

What are the presenting symptoms of Huntington’s?

Answer 7

• cognitive decline
  
  • presents as poor performance at work/school
• personality change
  
  • irritability/anger outbursts
  • impulsiveness
  • poor libido
• chorea
  
  • hands, trunk, limbs, facial expressions
• twitching/restlessness
  
  • ~ affect sleep
• loss of coordination
• deficit in fine motor coordination
  
  • hands, speech,
• slowed rapid (saccadic) eye movements
• imbalance

Question 8

What are the presenting symptoms of juvenile Huntington’s?

Answer 8

• motor: ~ not have chorea but ~ be rigid or parkinsonian
• eyes: slow saccade (usually 1st sign)

Question 9

What occurs to rapid hand alternating in Huntington’s? (gross motor function)

Answer 9

may be normal, fine motor coordination is affected

Question 10

What motor sign may be seen in pts with more advanced Huntington’s?

Answer 10

Milkmaid’s grip

• variation in the intensity of a requested squeeze
• (form of motor impersistence)

Question 11

What are the signs of Huntington’s O/E?

Answer 11

Motor function - general

• chorea - test: recite serial 7s seated, with eyes closed, w/o adventitious movements of fingers/toes
• loss of fine motor coordination - test: finger tapping - slowing & irregular tempo
• motor impersistence - test: protrude tongue/ close eyes tightly <10 seconds - trouble maintaining maximal protrusion / lid closure
• twitching/restlessness at rest

Gait

• choreic
• impaired tandem walking

​Eye (saccade)

• slow saccade - test

Speech

• dysarthria

Cognition/emotion

• deficits - test: MMSE
• poor executive functioning

Question 12

Which cognitive deficit appears as Parkinson’s progresses?

Answer 12

memory deficits - progressive

• ST
• LT
• episodic
• procedural
• working

eventually –> becomes dementia

Question 13

What are the primary investigations for ?Huntington’s?

Answer 13

none, diagnosis = clinical

Question 14

Which investigations could be considered to confirm a clinical diagnosis of Huntington’s?

Answer 14

• genetic: CAG repeat testing
  
  • normal = <28 repeats
  • positive result = ≥40 CAG repeats on 1 of 2 alleles
  • intermediate result = 36-39 repeats
• Brain MRI/CT
  
  • evident caudate / striatal atrophy ~ be apparent