Huntingtons Flashcards
What is the definition of Huntington’s disease?
Huntington’s chorea is an autosomal dominant genetic neurodegenerative condition that causes a progressive deterioration in the nervous system.
What is chorea
Excessive limb jerking
What is the epidemiology of Huntington’s disease?
- HD is estimated to have a prevalence of 2-5 per 100,000 worldwide
- Usually presents in middle age
- It appears to be less common in asian populations where the normal number of CAG trinucleotide repeats is lower.
Huntingtons is trinucleotide repeat disorder, what is that?
involves a genetic mutation in the HTT gene on chromosome 4. The CAG repeat usually goes on x36.
What does CAG code for?
Glutamine
What do the mutated proteins do?
These mutated proteins aggregate within the neuronal cells of the caudate and putamen (dorsal striatum) of the basal ganglia causing neuronal cell death.
What happens over time in Huntingtons?
Neuronal cell death —-> loss of brain tissue volume ~~~> expansion of lateral ventricles ~~> damage leads to chorea
What is there specific loss of?
corpus striatum GABAergic and cholinergic neurones which results in decreased ACh and GABA synthesis. Without this, levels of dopamine increase leading to excessive movement
What is anticipation? Huntingtons displays it
Anticipation is a feature of trinucleotide repeat disorders.
Anticipation is where successive generations have morerepeatsin the gene, resulting in:
- Earlier age of onset
- Increased severity of disease
What happens in anticipation?
The expanded CAG repeats not only affect the huntingtin protein – they affect DNA replication itself. When copying the HTT gene, DNA polymerase can lose track of which CAG it’s on and so add extra CAGs. This is called repeat expansion and happens more frequently in the production of sperm than egg.
What else does Huntington’s have?
Full penetrance
So all genotypes will express it
What are the clinical manifestations for Huntingtons?
Patients are usually asymptomatic until symptoms begin around aged 30 to 50. It presents with an insidious, progressive worsening of symptoms.
- Typically begins with prodromal phase: cognitive, psychiatric or mood problems.
- Chorea(involuntary, abnormal movements, fidgety)
- Eye movement disorders
- Dysarthria: speech difficulties
- Dysphagia: swallowing difficulties
- Dementia
- Psychosis
- Peronality change
Cardinal features of Huntingtons
- Chorea
- Dementia
- Psychiatric problems
- Positive family history
What are the findings on examination for huntingtons?
- Abnormal eye movements
- Problems with initiating saccades
- Broken pursuit
- Chorea
Chorea = dance
Random, unpredictable
Pat often tries to make the movements look normal - Ataxia
Problems with heel to toe walking - Often additional “touch of parkinsonism”
Rigidity
Slowness of fine finger movements
What are the investigations for Huntington’s?
- Diagnosis is made in a specialist genetic centre using a genetic test for the faulty gene and identification of the number of CAG repeats.
- This involves pre-test and post-test counselling regarding the implications of the results.
What is the management for Huntington’s disease
- Post-test counselling: to help patients cope with diagnosis
- Genetic counsellingregarding relatives, pregnancy and children
- Involvement ofMDTin supporting and maintaining their quality of life (e.g. occupational therapy, physiotherapy and psychology)
- Speech and language therapywhere there are speech and swallowing difficulties
- Advanced directivesto document the patients wishes as the disease progresses
- End of lifecare planning
What medical treatment is given for symptomatic relief?
- For disordered movements
- Antipsychotics (e.g. olanzapine, neuroleptics like Haloperidol)
- Benzodiazepines (e.g. diazepam)
- Dopamine-depleting agents (e.g. tetrabenazine)
- For depression
- Antidepressants - SSRI/ Seroxate
- For Chorea
- Neuroleptic - Sulpiride
- For Aggression
- Risperidone
How can we treat the choratheotosis in Huntington’s disease?
Bilateral stimulation of the globus pallidus internus
Prognosis of Huntingtons
Huntington’s chorea is a progressive condition.
Life expectancy is around 15-20 years after the onset of symptoms.
As the disease progresses patients become more susceptible and less able to fight off illnesses. Death is often due to respiratory disease (e.g. pneumonia). Suicide is a more common cause of death than in the general population.
Triple repeating disorders
- Huntington disease: CAG repeat
- Myotonic dystrophy: CTG repeat
- Friedreich ataxia: GAA repeat
- Fragile X syndrome: CGG repeat
Age relevance of Huntingtons
<35 = no Huntingtons
35-55 = Huntingtons
60+ = Severe Huntingtons
