Huntington's Disease/Chorea

Related Subjects: | Dementia | Alzheimer Disease | Vascular Dementia | Frontotemporal dementia | Huntington's Disease/Chorea | Dementia with Lewy bodies | Creutzfeldt Jakob disease | Behavioural and Psychological Symptoms of Dementia

The disease is named after George Huntington, a doctor of Ohio who published a paper in 1872 based on observations of patients in the East Hampton's, Long Island. The disease could be traced back to a family who had emigrated to the US in 1630 from a small Anglian town in Suffolk, England. If interested read the excellent "Saturday" by Ian McEwan which features a character with Huntington's Chorea.

Rhythmic twirl of wrist
Hints at cruel genetic twist
CAG repeats
If child’s path trails parent’s fate
Younger would anticipate       Link to author

About

• Autosomal dominant inheritance
• Choreiform movement disorder in patient aged 30-50
• Cognitive issues are more disabling than chorea
• There is often a family history

Aetiology

• The Mutant HTT gene is at 4p.16.3 and encodes the protein *huntingtin*
• Disease is almost certain with expanded (over 42) CAG trinucleotide repeats.
• CAG (cytosine-adenine-guanine) codes for glutamine
• The translated result is long tracts of glutamine residues
• Main structures affected are the caudate and putamen of the basal ganglia
• Paternally inherited disease may come on earlier and produce a variant with a Parkinsonian picture in childhood

There is a juvenile form of the illness which affects children and young adults under 21 at the point of diagnosis in which Rigidity, spasticity and dystonia are seen early

Clinical

• Restless and fidgets, extra movements proceeding over time to chorea
• Slowness of movements eventually and chorea eventually declines
• Late disease has Rigidity, spasticity and dystonia but this is seen much earlier in those with childhood onset in which they are often present from the beginning
• Onset at earlier age with each generation - anticipation
• Difficulty multitasking unable to organise and concentrate and prioritorise
• Subcortical dementia and epilepsy is also a feature
• Increased blink frequency (opposite of Parkinson's disease)
• Slow eye movements, balance problems, late stage dysphagia
• Psychiatric features include mood swings, anger and poor self-control.
• Obsessive compulsive and even psychotic episodes, depression, anxiety
• Episodic anger and irritability, impulsive
• There is a Westphal variant which demonstrates increased rigidity and parkinsonism and is commoner in children

Investigations

• FBC, U&E, LFTs
• CT/MRI shows decrease in size of caudate and putamen.
• PET scan shows decreased metabolism in an anatomically normal caudate in early disease
• Post mortem studies show significant atrophy of both the cerebral cortex and the corpus striatum.
• There is significant cell loss in the caudate and putamen.
• Genetic testing is now available before the onset of symptoms - ethical questions. Testing is only available at regional genetics clinics, which are located throughout England and Wales. GPs can arrange a referral. For more information go to www.hda.org.uk

Differentials

• Sydenham's chorea
• Wilson's disease

Management

• Management largely supportive and genetic counselling for the family affected
• Treatment of the chorea can involve Haloperidol [US Haldol], Sulpiride and dopamine depleting drugs such as Tetrabenazine to try and induce parkinsonism which might be worse than the chorea
• SSRI's may be useful to treat depression and Sodium Valproate and Carbamazepine may help as mood stabilisers.

References

• A Guide for Family doctors
• Review article Huntington's Disease/Chorea