What is Huntington disease?
Huntington disease (HD) is a progressive, neurodegenerative genetic disorder characterized by involuntary movements (chorea), lack of coordination, cognitive decline, and behavioral/personality changes. The symptoms of HD are as a result of loss of neurons (nerve cells) in certain regions of the brain and usually develop in affected individuals between the ages of 30 and 50 years, although there is a form that affects children…
Huntington disease (HD) is a progressive, neurodegenerative genetic disorder characterized by involuntary movements (chorea), lack of coordination, cognitive decline, and behavioral/personality changes. The symptoms of HD are as a result of loss of neurons (nerve cells) in certain regions of the brain and usually develop in affected individuals between the ages of 30 and 50 years, although there is a form that affects children called juvenile-onset Huntington disease. The disease affects men and women alike, with a higher frequency among populations of European descent. In Western countries, an estimated 5 to 7 people per 100,000 are affected by HD. The number may actually be higher, however, because many people who have the Huntington gene do not yet have symptoms.
Huntington disease is an autosomal dominant disorder involving a defective gene on chromosome 4. That means that only one copy of that abnormal gene is needed to cause the disease in an affected person, inherited from either of that person’s parents. The mutation associated with HD is an expansion of the trinucleotide repeat sequence “CAG” in the IT-15 gene (HD gene), which encodes the huntingtin protein. Although genes often have repeats as part of their sequence, when the number of repeats becomes too large, it can lead to disease. In the case of HD, instead of a normal repeat of 11 to 29 times, this section of DNA is repeated 40 to more than 80 times. This type of mutation (i.e., expansion of repeat sequences) can also be seen in a number of other genetic diseases, such as Fragile X syndrome.
In general, there is a direct 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. In addition to this, mutated alleles are genetically unstable and have a tendency to undergo further expansion as they are transmitted to future generations, increasing the disease severity in subsequent generations. This phenomenon is known as anticipation.
About Huntington Disease
Signs and Symptoms
The signs and symptoms of HD are wide-ranging and can vary from person to person. Generally, symptoms become more severe as the disease progresses. Some common symptoms are listed below.
- Rapid, involuntary movements of the fingers, limbs, and facial muscles (chorea); this varies in severity from mild twitching to more severe thrashing as the disease progresses.
- Rapid movement of the eye used to focus from one object to another (reduced saccadic motion of the eyes)
- 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; disorganized 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:
- Difficulty swallowing (dysphagia) 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 such as wheelchairs
Children with juvenile-onset HD have rigidity, slow movements, and tremors that are similar to symptoms of Parkinson disease.
To diagnose Huntington disease, a healthcare practitioner may perform a neurological exam and ask about the person’s family history and symptoms. Imaging tests may be performed to look for signs of the disease and genetic testing can be done to determine if the person has the abnormal gene.
Molecular genetic testing
Molecular genetic testing is used to determine if a person has an allele, or gene variant, that predisposes to Huntington disease. It can be used to confirm a clinical diagnosis of HD and for predictive testing in asymptomatic individuals. The most common approach used is direct mutation analysis, which involves analysis of the person’s DNA to estimate the length of the CAG repeat mutation.
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, that is, in those with a family history of HD. This is done using molecular genetics testing as described above. Predictive testing, in affected families, is also used to determine the disease status in females of child-bearing age and pregnant women to assess the risk of passing the disease to their children. Similarly, prenatal testing can also be done to determine if a fetus is affected.
Those who are considering genetic testing may want to consult with a genetic counselor, who can help them to better understand the pros and cons of this type of testing.
These imaging tests can provide an image of the brain showing areas of degeneration. They are not very useful, however, in early-stage HD because they are unable to show small regions of brain deterioration.
- CT scan
- PET scan
For more on imaging studies, see the web site RadiologyInfo.org.
Currently, there is no treatment available for the cure or prevention of Huntington disease. Most of the treatment and interventions available are supportive. These include medications to help control erratic behavior and movements, physical and occupational therapy as well as therapy for speech and in help swallowing, and counseling and caregiver support. In 2008, the drug tetrabenazine became the first medication approved by the U.S. Food and Drug Administration (FDA) to treat the involuntary movements characteristic of HD. Research is ongoing in an effort to develop targeted drug therapies for this disease. Current research pursuing gene therapies for treating HD could eventually prove useful; however, the technology is still in its infancy.
Sources Used in Current Review
Mayo Clinic. 2014. Huntington’s Disease. Available online at http://www.mayoclinic.org/diseases-conditions/huntingtons-disease/basics/tests-diagnosis/con-20030685. Accessed September 24, 2015.
National Health Services. 2014. NHS Choices. Huntington’s Disease. Available online at http://www.nhs.uk/conditions/Huntingtons-disease/Pages/Introduction.aspx. Accessed September 24, 2015.
World Health Organization. 2015. Genes and Human Disease. Available online at http://www.who.int/genomics/public/geneticdiseases/en/index2.html. Accessed September 24, 2015.
HD Buzz. 2013. Could a new “jaw-dropping breakthrough” help treat Huntington’s Disease? Available online at http://en.hdbuzz.net/149. Accessed September 24, 2015.
HDBuzz. 2013. How long is too long? Rethinking the Huntington’s Disease “gray area.” Available online at http://en.hdbuzz.net/133. Accessed September 24, 2015.
Sources Used in Previous Reviews
Imariso, S., J. Carmichael, V. Korolchuk, C.W. Chen, S. Saiki, C. Rose, G. Krishna, J.E. Davis, E. Ttofi, B.R. Underwood and D.C. Rubinstein. Huntington’s Disease: From Pathology and Genetics to potential therapies. Journal of Biochemistry. 2008; 412(1):191-209.
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.
MedlinePlus Medical Encyclopedia. Huntington’s disease. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000770.htm. Accessed July 2011.
MayoClinic.com. Huntington’s disease. Available online at http://www.mayoclinic.com/health/huntingtons-disease/DS00401. Accessed March 2011.
National Institute of Neurological Disorders and Stroke. Huntington’s Disease Information Page. Available online at http://www.ninds.nih.gov/disorders/huntington/huntington.htm. Accessed March 2011.
Genome.gov. Learning About Huntington’s Disease. Available online at http://www.genome.gov/10001215. Accessed July 2011.