Clinical Aspects of Huntington's Disease Flashcards
What are the 3 main components of Huntington Disease?
1) . Movement disorder
2) . Psychiatric disturbance
3) . Dementia
What is the prevalence of Huntington disease?
Huntington disease has a prevalence if 4-10 per 10,000.
What feature may Huntington disease display that may not be seen in a small family?
Huntington disease may display anticipation in successive generations. However, this may not be evident in a small family.
What features may you observe on the examination of post-mortem scans of an individual with Huntington disease?
- Striking degeneration of the basal ganglia and caudate nuclear in particular.
- The brain is generally smaller, especially the frontal lobes.
Describe the clinical features of Huntington disorder.
1) . Involuntary movement disorder - chorea and later dystonia, bradykinesia and decreased voluntary movements. May go through periods of increased involuntary movements followed by periods of rigidity.
2) . Psychiatric disturbance - mood swings, paranoid ideation, rigid thought processes (e.g. problems forward planning) and depression. Psychiatric symptoms may be present before HD is diagnosed and may be what prompts the individual to seek medical help.
3) . Dementia.
4) . Slurred speech and swallowing difficulties. Both tend to be later onset in Huntingtons.
5) . Weight loss.
6) . Runs a course over 15-20 years.
7) . Peak age of onset 40-45 years.
8) . 4.5% have an onset under 20yrs (juvenile HD) and 8% over 60yrs.
9) . Due to their insidious nature, patients and families may not recognise their symptoms even if they know they are at risk.
What is the peak age of onset for HD?
Peak age of onset 40-45 years (30-60yrs is the normal range).
What percentage of HD cases can be classified as juvenile HD?
4.5% have an onset under 20yrs (juvenile HD).
Approximately what % of HD cases occur over 60 yrs?
8% of HD cases have an onset over 60 years.
What conditions may be included in the differential diagnosis for HD?
May consider a number of other conditions if an individual has no family history of HD but is presenting with chorea.
1) . Benign familial chorea - onset in early childhood of isolated chorea, AD. Don’t get the other psychiatric disturbances or the progression associated with HD.
2) . Dentatorubropallidoluysian Atrophy (DRPLA) - choreoathetosis, ataxia, myoclonus and dementia, AD, also a triplet repeat condition. Rare condition. When samples come in from neurology for HD analysis they will usually request DRLPA at the same time because the phenotypes are so similar.
3) . Neuroacanthosis - AR movement disorder, chorea and dystonia but dementia is not a prominent feature. Blood film for acanthocytes (so won’t come through the molecular lab) .
4) . Wilson Disease - AR, onset in mid childhood - differential for juvenile HD mainly.
5) . Spinocerebellar Ataxia - Ataxia but without chorea, psychiatric symptoms and dementia absent or mild.
What is the differential diagnosis for juvenile HD?
Wilsons Disease.
Describe HD Allele Classification.
- Normal <27
- Intermediate = 27-35 repeats
- HD allele - reduced penetrance = 36-39 repeats
- HD allele >39 repeats
What is the intermediate range for an HD allele and what problems does it present?
The intermediate range for an HD allele is between 27 and 35 repeats. Intermediate range is difficult as it may be unstable in future generations.
What is the reduced penetrance range for an HD allele and what problems does it present?
The reduced penetrance range for an HD allele is between 36 and 39 repeats.
Results that land in the reduced penetrance range carry a risk of symptoms later in life - there are study figures giving the percentage of individuals who become symptomatic depending on age and repeat size.
These issues are always discussed with individuals going through a pre-symptomatic test.
Describe the process of HD testing from a clinical genetics perspective.
- Most diagnostic tests are performed by neurologists, often as part of a battery of investigations unless there is a known family history to target analysis.
- All predictive testing is performed within the clinical genetics team by clinical geneticists and clinical genetic counsellors.
- The predictive testing protocol involves 3 counselling sessions involving 2 members of staff over a period of months.
- Checklist of issues which must be covered including past mental health, coping mechanisms, insurance implications, family dynamics, implications for employment and children.
- There are tables giving 95% CIs for age of onset based on repeat size and residual risk of carrying the gene in a disease free individual at a given age but these are rarely used in the PST discussions. Experience shows that these tables can give false reassurance or focus the PST discussions on statistics rather than the individual’s motivation for having a test and coping strategies.
- Only about 15-25% of individuals at 50% risk come forward for a PST and many decide against a test or delay after 1 or 2 appointments.
- Cases are discussed with the GP wherever possible so that they are aware of the disclosure appointment and can highlight any past relevant issues.
- In some cases, referral to a psychiatrist for further assessment is added to the protocol.
- A PST is only available to adults.
- Written informed consent is taken for an HD PST.
- Follow up contact and support is offered after results are given.
What issues must be covered when an individual is being assessed for HD testing by the clinical genetics team?
Checklist of issues which must be covered including past mental health, coping mechanisms, insurance implications, family dynamics, implications for employment and children.
