Last Review Date: March 1, 2018
Huntington’s disease (HD) or chorea is a progressive, neurodegenerative genetic disorder characterised by chorea (involuntary movements), in-coordination, cognitive decline and behavioural/personality changes. In general, develop in adults between the ages of 30-50 years, although a small proportion (≈5%) show before the age of 20 years. This is referred to as Juvenile-onset Huntington’s disease. The symptoms of HD are as a result of loss of neurons (brain cells) in certain regions of the brain.
Huntington’s disease is an disorder. The mutation associated with HD is an expansion of the trinucleotide repeat sequence, CAG, in the IT-15 (HD gene) which encodes the huntingtin . Although genes often have repeats as part of their sequence, when the number of repeats becomes too large, it can lead to disease. The result of this expansion is defects or deficiencies in the huntingtin protein leading to disease. This type of mutation (i.e. ) can also be seen in a number of other genetic diseases such as .
Four classes of HD have been described:
- The normal allele containing ≤ 26 CAG repeats (less than or equal to 26 CAG repeats).*
- Alleles containing between 27-35 CAG repeats. Individuals with these alleles will not develop HD but there is the potential to expand into the disease range in the next generation.
- Intermediate alleles containing between 36-39 repeats.*
Individuals with these alleles may or may not develop symptoms of HD.
These alleles are described as having reduced or incomplete penetrance.
- The HD allele containing ≥ 40 CAG repeats (greater than or equal to 40 CAG repeats).*
All individuals with these HD alleles will eventually develop symptoms of HD, i.e. having high or full penetrance.
* Note that these numbers may vary slightly between different laboratories and regions.
In general, there is an inverse relationship between the number of repeats and the severity of disease, that is, the larger the repeat size, the more severe the symptoms and the earlier the onset of disease. However, the repeat size cannot be used to indicate the age of onset. In addition to this, mutated alleles are genetically unstable and have a tendency to undergo further expansion more commonly through paternal transmission to future generations, increasing the disease severity in subsequent generations. This phenomenon is known as anticipation.
Huntington’s disease tends to have a higher frequency in populations of European decent and in Australia affects between 6-7 people in every 100,000. HD remains prevalent in the population because of its relatively late onset, i.e. affected individuals are usually during their reproductive years, allowing the mutation to be silently passed onto subsequent generations.
For further explanation on patterns of inheritance see Genetic testing
The signs and symptoms of HD are widespread and can vary from person to person. Generally, symptoms become more severe as the disease progresses. Some common symptoms include:
- Chorea (rapid, involuntary movements of the fingers, limbs and facial muscles). This varies in severity from mild twitching to more severe thrashing as the disease progresses
- Reduced saccadic motion of the eyes (rapid movement of the eye used to focus from one object to another)
- Loss of motor coordination and fine motor movements e.g. difficulty writing.
- Reduced short-term memory
- Concentration impairment
- Difficulty with communication e.g. slow, slurred speech; difficulty in finding words; disorganised speech and sentence construction.
- Change in personal hygiene and habits
- Unusually anxious behaviour
- Irritability and aggression
- Depression, particularly in later stages.
A number of complications can arise in late-stage HD including:
- Dysphagia (difficulty swallowing) resulting in weight loss and increased risk of choking
- Increased risk of respiratory disease such as pneumonia
- Incontinence and other urinary tract problems e.g. infections
- Falls and difficulty walking requiring the use of assist devices e.g. wheelchairs.
Non-laboratory evaluation includes a detailed family history and clinical assessments of the signs and symptoms of HD. The number and types of tests carried out will vary depending on the organisation and progression of disease. These tests are only useful in patients exhibiting symptoms of HD.
Tests to assess motor, cognitive and behavioural patterns.
A collection of simple, clinical tests performed by doctors or nurses to determine
the presence and severity of motor, cognitive and behavioural symptoms.
Provides an image of the brain showing areas of degeneration. Imaging tests are not very useful
in early stage HD because they are unable to show small regions of neural deterioration.
Molecular genetics testing
Molecular genetics testing is used to determine if the patient has an , or gene variant, that predisposes to Huntington’s disease. It can be used to confirm a clinical diagnosis of HD and for predictive testing in asymptomatic patients. The most common approach used is direct mutation analysis which involves analysis of the patients to estimate the length of the CAG repeat mutation. There are a number of different methodologies adopted of which the most widely used are based on (polymerase chain reaction) and for large CAG expansion either analysis or Triplet-repeat primed PCR (TP PCR) is used
Routine screening of the general population is not recommended, especially due to the lack of effective intervention to stop the onset of disease. However, it should be considered in individuals at an increased risk of HD, that is, in those with a family history of HD. This is done using molecular genetic testing as described above. Predictive (presymptomatic) testing, is offerd to individuals in affected families who are at a 50-25% risk of developing HD. Testing during pregnancy can be done to determine if a fetus is affected (prenatal testing) via an amniocentesis or chorionic villus sample. Preimplantation genetic diagnosis (PGD) may be a valuable option for couples who wish to avoid transmitting the disease without revealing their own status and to avoid termination of a pregnancy.
Currently there is no treatment available for the cure or prevention of Huntington's disease. Most of the treatment and interventions available are supportive.
Counselling and care-giver support:
- Information regarding the expected signs and symptoms and how they can be recognised and effectively managed.
- Safety advice e.g. when to give up driving or working.
- Directing families to community support groups and relevant government agencies.
- Speech therapy, physiotherapy, swallowing therapy etc.
- Family planning services.
On this site
Features: Genetic testing
Elsewhere on the web
HOPES: Huntington's Outreach Project (USA)
Healthdirect Australia: Huntington's Disease
NOTE: This article is based on research that utilises the sources cited here as well as the collective experience of the Lab Tests Online-AU Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources used in current review
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Margolis, R.L. and C.R. Christopher. Diagnosis of Huntington Disease. Clinical Chemistry 2003; 49:1726-1732.
Myers, R.H. Huntington’s Disease Genetics. Journal of the American Society for Experimental NeuroTherapeutics 2004; 1(2): 255-262.
Potter,N.T., E.B. Spector and T.W. Prior. 2006. Standards and Guidelines for Clinical Genetics Laboratories: Technical Standards and Guidelines for Huntington Disease. American College of Medical Genetics. Available online at http://www.acmg.net/Pages/ACMG_Activities/stds-2002/HD.htm. Accessed February 2011.
Warby, S.C., R.K. Graham and M.R. Hayden. GeneReviews: Huntington Disease. National Centre for Biotechnology Information. Available online at http://www.ncbi.nlm.nih.gov/books/NBK1305/#huntington.References. Accessed February 2011.