Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability. Huntington's disease causes a progressive breakdown of nerve cells in the brain. Find out about symptoms, diagnosis and treatment. Huntington's disease (HD), also known as Huntington's chorea, is an inherited disorder that results in death of brain cells. The earliest symptoms are often subtle.
Embryos produced using in vitro fertilization may be genetically tested for HD using preimplantation genetic diagnosis PGD. This technique, where one or two cells are extracted from a typically 4- to 8-cell embryo and then tested for the genetic abnormality, can then be used to ensure embryos affected with HD genes are not implanted, and therefore any offspring will not inherit the disease. Some forms of preimplantation genetic diagnosis—non-disclosure or exclusion testing—allow at-risk people to have HD-free offspring without revealing their own parental genotype, giving no information about whether they themselves are destined to develop HD.
In exclusion testing, the embryos' DNA is compared with that of the parents and grandparents to avoid inheritance of the chromosomal region containing the HD gene from the affected grandparent. In non-disclosure testing, only disease-free embryos are replaced in the uterus while the parental genotype and hence parental risk for HD are never disclosed. It is also possible to obtain a prenatal diagnosis for an embryo or fetus in the womb, using fetal genetic material acquired through chorionic villus sampling.
An amniocentesis can be performed if the pregnancy is further along, within 14—18 weeks. This procedure looks at the amniotic fluid surrounding the baby for indicators of the HD mutation. The parents can be counseled on their options, which include termination of pregnancy , and on the difficulties of a child with the identified gene. In addition, in at-risk pregnancies due to an affected male partner, non-invasive prenatal diagnosis can be performed by analyzing cell-free fetal DNA in a blood sample taken from the mother via venipuncture between six and twelve weeks of pregnancy.
Other autosomal dominant diseases that can be misdiagnosed as HD are dentatorubral-pallidoluysian atrophy and neuroferritinopathy. There are also autosomal recessive disorders that resemble sporadic cases of HD. These include chorea acanthocytosis and pantothenate kinase-associated neurodegeneration. One X-linked disorder of this type is McLeod syndrome. There is no cure for HD, but there are treatments available to reduce the severity of some of its symptoms.
Weight loss and eating difficulties due to dysphagia and other muscle discoordination are common, making nutrition management increasingly important as the disease advances. This is a feeding tube, permanently attached through the abdomen into the stomach, which reduces the risk of aspirating food and provides better nutritional management. People with Huntington's disease may see a physical therapist for non-invasive and non-medication-based ways of managing the physical symptoms.
Physical therapists may implement fall risk assessment and prevention, as well as strengthening, stretching, and cardiovascular exercises. Walking aids may be prescribed as appropriate. Physical therapists also prescribe breathing exercises and airway clearance techniques with the development of respiratory problems.
Participation in rehabilitation programs during early to middle stage of the disease may be beneficial as it translates into long term maintenance of motor and functional performance. Rehabilitation during the late stage aims to compensate for motor and functional losses. Additionally, an increasing number of people with Huntington's disease are turning to palliative care, which aims to improve quality of life through the treatment of the symptoms and stress of serious illness, in addition to their other treatments.
Tetrabenazine was approved in for treatment of chorea in Huntington's disease in the EU, and in in the US. Psychiatric symptoms can be treated with medications similar to those used in the general population.
The families of individuals, and society at large, who have inherited or are at risk of inheriting HD have generations of experience of HD, but may be unaware of recent breakthroughs in understanding the disease, and of the availability of genetic testing. Genetic counseling benefits these individuals by updating their knowledge, seeking to dispel any unfounded beliefs that they may have, and helping them consider their future options and plans.
Also covered is information concerning family planning choices, care management, and other considerations. A longer repeat results in an earlier age of onset and a faster progression of symptoms. The largest risk is pneumonia , which causes death in one third of those with HD. As the ability to synchronize movements deteriorates, difficulty clearing the lungs and an increased risk of aspirating food or drink both increase the risk of contracting pneumonia.
The second greatest risk is heart disease , which causes almost a quarter of fatalities of those with HD. It is unclear to what extent suicidal thoughts are influenced by behavioral symptoms, as they signify sufferers' desires to avoid the later stages of the disease.
The late onset of Huntington's disease means it does not usually affect reproduction. The rate of occurrence is highest in peoples of Western European descent, averaging around 7 per , people, and is lower in the rest of the world; e. A epidemiological study of the prevalence of Huntington's disease in the UK between and found that the average prevalence for the UK was Until the discovery of a genetic test , statistics could only include clinical diagnosis based on physical symptoms and a family history of HD, excluding those who died of other causes before diagnosis.
These cases can now be included in statistics; and, as the test becomes more widely available, estimates of the prevalence and incidence of the disorder are likely to increase.
Although Huntington's has been recognized as a disorder since at least the Middle Ages , the cause has been unknown until fairly recently. Huntington's was given different names throughout this history as understanding of the disease changed. Originally called simply 'chorea' for the jerky dancelike movements associated with the disease, HD has also been called "hereditary chorea" and "chronic progressive chorea". Waters described "a form of chorea, vulgarly called magrums", including accurate descriptions of the chorea, its progression, and the strong heredity of the disease.
The first thorough description of the disease was by George Huntington in Examining the combined medical history of several generations of a family exhibiting similar symptoms, he realized their conditions must be linked; he presented his detailed and accurate definition of the disease as his first paper.
Huntington described the exact pattern of inheritance of autosomal dominant disease years before the rediscovery by scientists of Mendelian inheritance. When either or both the parents have shown manifestations of the disease But if by any chance these children go through life without it, the thread is broken and the grandchildren and great-grandchildren of the original shakers may rest assured that they are free from the disease.
Sir William Osler was interested in the disorder and chorea in general, and was impressed with Huntington's paper, stating that "In the history of medicine, there are few instances in which a disease has been more accurately, more graphically or more briefly described.
During the rediscovery of Mendelian inheritance at the turn of the 20th century, HD was used tentatively as an example of autosomal dominant inheritance. Researchers have found contrary evidence; for instance, the community of the family studied by George Huntington openly accommodated those who exhibited symptoms of HD. The search for the cause of this condition was enhanced considerably in , when the Hereditary Disease Foundation HDF was created by Milton Wexler , a psychoanalyst based in Los Angeles , California , whose wife Leonore Sabin had been diagnosed earlier that year with Huntington's disease.
The foundation was involved in the recruitment of over scientists in the Huntington's Disease Collaborative Research Project who over a year period worked to locate the responsible gene. Thanks to the HDF, the ongoing US-Venezuela Huntington's Disease Collaborative Research Project was started in , and reported a major breakthrough in with the discovery of the approximate location of a causal gene.
It involved over 18, people—mostly from a single extended family. Among other innovations, the project developed DNA -marking methods which were an important step in making the Human Genome Project possible. In the same time frame, key discoveries concerning the mechanisms of the disorder were being made, including the findings by Anita Harding 's research group on the effects of the gene's length.
Modelling the disease in various types of animals, such as the transgenic mouse developed in , enabled larger scale experiments. As these animals have faster metabolisms and much shorter lifespans than humans, results from experiments are received sooner, speeding research.
The discovery that mHTT fragments misfold led to the discovery of the nuclear inclusions they cause. These advances have led to increasingly extensive research into the proteins involved with the disease, potential drug treatments, care methods, and the gene itself.
The condition was formerly called 'Huntington's chorea' but this term has been replaced by 'Huntington's disease' because not all patients develop chorea and due to the importance of cognitive and behavioral problems. Huntington's disease, particularly the application of the genetic test for the disease, has raised several ethical issues.
The issues for genetic testing include defining how mature an individual should be before being considered eligible for testing, ensuring the confidentiality of results, and whether companies should be allowed to use test results for decisions on employment, life insurance or other financial matters.
There was controversy when Charles Davenport proposed in that compulsory sterilization and immigration control be used for people with certain diseases, including HD, as part of the eugenics movement. Some HD research has ethical issues due to its use of animal testing and embryonic stem cells. The development of an accurate diagnostic test for Huntington's disease has caused social, legal, and ethical concerns over access to and use of a person's results.
There is consensus for testing only individuals who are considered cognitively mature, although there is a counter-argument that parents have a right to make the decision on their child's behalf. With the lack of an effective treatment, testing a person under legal age who is not judged to be competent is considered unethical in most cases.
There are ethical concerns related to prenatal genetic testing or preimplantation genetic diagnosis to ensure a child is not born with a given disease. This would require parts of the process to be kept secret from the parent. In , after experiencing HD in his wife's family, Dr. Milton Wexler was inspired to start the Hereditary Disease Foundation HDF , with the aim of curing genetic illnesses by coordinating and supporting research.
Since then, support and research organizations have formed in many countries around the world and have helped to increase public awareness of HD. A number of these collaborate in umbrella organizations, like the International Huntington Association and the European HD network.
The largest funder of Huntington's disease research globally, in terms of financial expenditure,  is the CHDI Foundation , a US non-profit biomedical foundation that aims to "rapidly discover and develop drugs that delay or slow Huntington's disease". Research into the mechanism of HD has focused on identifying the functioning of HTT, how mHTT differs or interferes with it, and the brain pathology that the disease produces.
Research is conducted using in vitro methods, animal models and human volunteers. Animal models are critical for understanding the fundamental mechanisms causing the disease and for supporting the early stages of drug development. Research is being conducted on many different approaches to prevent Huntington's disease or slow its progression.
Disease-modifying strategies can be broadly grouped into three categories: In addition, novel therapies to improve brain functioning are under development; these seek to produce symptomatic rather than disease-modifying therapies, and include phosphodiesterase inhibitors.
Gene silencing aims to reduce the production of the mutant protein, since HD is caused by a single dominant gene encoding a toxic protein. Gene silencing experiments in mouse models have shown that when the expression of mHTT is reduced, symptoms improve.
One way of accomplishing this is to identify polymorphisms present on only one allele and produce gene silencing drugs that target polymorphisms in only the mutant allele. Among the approaches aimed at improving cell survival in the presence of mutant huntingtin are correction of transcriptional regulation using histone deacetylase inhibitors , modulating aggregation of huntingtin, improving metabolism and mitochondrial function and restoring function of synapses.
Stem cell therapy is the replacement of damaged neurons by transplantation of stem cells into affected regions of the brain. Experiments have yielded mixed results using this technique in animal models and preliminary human clinical trials. Several clinical trials of new experimental treatments are underway and planned in Huntington's disease. Compounds that have failed to prevent or slow progression of Huntington's disease in human trials include remacemide , coenzyme Q10 , riluzole , creatine , minocycline , ethyl-EPA , phenylbutyrate and dimebon.
From Wikipedia, the free encyclopedia. List of Huntington's disease media depictions. Archived from the original on 27 July Retrieved 19 July A Journey through History". Tremor and Other Hyperkinetic Movements. Archived from the original on 4 July Archived from the original on 19 November Retrieved 18 November Huntington's Disease Society of America. Archived from the original on 9 April Retrieved 17 March The Journal of Neuropsychiatry and Clinical Neurosciences.
Archived from the original on 10 February Retrieved 12 March Huntington's Outreach Project for Education, at Stanford. If one of your parents has Huntington's disease, you have a 50 percent chance of getting it. A blood test can tell you if have the HD gene and will develop the disease.
Genetic counseling can help you weigh the risks and benefits of taking the test. There is no cure. Medicines can help manage some of the symptoms, but cannot slow down or stop the disease.
Huntington's Disease Also called: Learn More Related Issues Genetics. See, Play and Learn Videos and Tutorials.
Huntington disease HD is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Mean age at onset of symptoms is years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school Juvenile Huntington disease, JHD; see this term.
The classic sign is chorea that gradually spreads to all muscles. Other unwanted movements include tics, comparable to those seen in Tourette syndrome see this term , but these are fairly rare. Cerebellar signs can appear sporadically, similar to the presence of hypo- and hypermetria. Other less well-known, but prevalent and often debilitating features of HD include unintended weight loss, sleep- and circadian rhythm disturbances and autonomic nervous system dysfunction.
Dysarthria and dysphagia become very prominent during the course of the disease. Talking and swallowing gradually become more problematic leading to choking at any time in some patients. All patients develop hypokinesia and rigidity leading to bradykinesia and severe akinesia. All psychomotor processes become severely impaired. Patients also experience cognitive decline. Psychiatric symptoms are very common in the early stage of the disease, often prior to onset of motor symptoms.
Suicide occurs more frequently in early symptomatic patients and also in premanifest gene carriers. The most risky periods for suicide are around the time of the gene test and when independence starts to diminish. HD is caused by an elongated CAG repeat 36 repeats or more on the short arm of chromosome 4 4p
What Is Huntington’s Disease?
Huntington's disease – learn about HD symptoms, diagnosis, causes and treatments and how this disorder relates to Alzheimer's and other dementias. Huntington's disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. It deteriorates a person's physical and. Read the accounts of people from all walks of life affected by Huntington's disease. Friends, family, caregivers, volunteers, and those afflicted with HD share their.