Huntington's or Huntington disease (HD), also known as Huntington's chorea, is a fatal neurodegenerative disease that is usually inherited. It typically presents as a triad of progressive psychiatric, cognitive, and motor symptoms. The earliest symptoms are often subtle problems with mood or mental/psychiatric abilities, which precede the motor symptoms for many people. The definitive physical symptoms, including a general lack of coordination and an unsteady gait, eventually follow. Over time, the basal ganglia region of the brain gradually becomes damaged.
The disease is primarily characterized by a distinctive hyperkinetic movement disorder known as chorea. Chorea classically presents as uncoordinated, involuntary, "dance-like" body movements that become more apparent as the disease advances. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia, depression, apathy, and impulsivity at times. The specific symptoms vary somewhat among cases. Symptoms can start at any age, but are usually first seen around the age of 40. The disease may develop earlier in each successive generation. About eight percent of cases start before the age of 20 years, and are known as juvenile HD, which typically present with the slow movement symptoms of Parkinson's disease rather than those of chorea.
HD is typically inherited from an affected parent, who carries a mutation in the huntingtin gene (HTT), which encodes the huntingtin protein. However, up to 10% of cases are due to a new mutation. Expansion of CAG repeats (known as a trinucleotide repeat expansion) in the gene coding for the huntingtin protein results in an abnormal mutant protein (mHTT), which gradually damages brain cells through a number of possible mechanisms. The mutant protein is dominant, so having one parent who is a carrier of the trait is sufficient to trigger the disease in their children. Diagnosis is by genetic testing, which can be carried out at any time, regardless of whether or not symptoms are present. This fact raises several ethical debates: the age at which an individual is considered mature enough to choose testing; whether parents have the right to have their children tested; and managing confidentiality and disclosure of test results.
No cure for HD is known, and full-time care is required in the later stages. Treatments can relieve some symptoms and possibly improve quality of life. The best evidence for treatment of the movement problems is with tetrabenazine. HD affects about 4 to 15 in 100,000 people of European descent. It is rare among the Finnish and the Japanese, while the incidence in Africa is unknown. The disease affects males and females equally. Complications such as pneumonia, heart disease, and physical injury from falls reduce life expectancy; fatal aspiration pneumonia is commonly cited as the ultimate cause of death for those with the condition. Suicide is the cause of death in about 9% of cases. Death typically occurs 15–20 years from when the disease was first detected.
The earliest known description of the disease was in 1841 by the American physician Charles Oscar Waters. The condition was described in further detail in 1872 by the American physician George Huntington. The genetic basis was discovered in 1993 by an international collaborative effort led by the Hereditary Disease Foundation. Research and support organizations began forming in the late 1960s to increase public awareness, provide support for the afflicted and their families, and promote research. Research directions include determining the exact mechanism of the disease, improving animal models to aid with research, testing of medications and their delivery to treat symptoms or slow the progression of the disease, and studying procedures such as stem-cell therapy with the goal of replacing damaged or lost neurons.
Signs and symptoms of Huntington's disease most commonly become noticeable between the ages of 30 and 50 years, but they can begin at any age and present as a triad of motor, cognitive, and psychiatric symptoms. When developed in an early stage, it is known as juvenile Huntington's disease. In 50% of cases, the psychiatric symptoms appear first. These can precede the motor symptoms by many years. Disease progression is often described in early stages, middle stages and late stages with an earlier prodromal phase. In the early stages, subtle personality changes, problems in cognition and physical skills, irritability and mood swings occur, all of which may go unnoticed. Almost everyone with HD eventually exhibits similar physical symptoms, but the onset, progression, and extent of cognitive and behavioral symptoms vary significantly between individuals.
The most characteristic initial physical symptoms are jerky, random and uncontrollable movements called chorea. Many people are not aware of their involuntary movements, or impeded by them. Chorea may be initially exhibited as general restlessness, small unintentionally initiated or uncompleted motions, lack of coordination, or slowed saccadic eye movements. These minor motor abnormalities usually precede more obvious signs of motor dysfunction by at least three years. The clear appearance of symptoms such as rigidity, writhing motions, or abnormal posturing appear as the disorder progresses. These are signs that the system in the brain that is responsible for movement has been affected. Psychomotor functions become increasingly impaired, such that any action that requires muscle control is affected. When muscle control is affected, such as with rigidity or muscle contractures, it is known as dystonia. Dystonia is a neurological hyperkinetic movement disorder that results in twisting or repetitive movements that may resemble a tremor. Common consequences are physical instability, abnormal facial expression, and difficulties chewing, swallowing and speaking. Sleep disturbances and weight loss are also associated symptoms, and difficulty eating may cause weight loss and malnutrition. Juvenile HD generally progresses at a faster rate with greater cognitive decline, and chorea is exhibited briefly, if at all. The Westphal variant of slowness of movement, rigidity, and tremors is more typical in juvenile HD, as are seizures.
Cognitive abilities are progressively impaired and tend to generally decline into dementia. Especially affected are executive functions, which include planning, cognitive flexibility, abstract thinking, rule acquisition, initiation of appropriate actions, and inhibition of inappropriate actions. Different cognitive impairments include difficulty focusing on tasks, lack of flexibility, a lack of impulse, a lack of awareness of one's own behaviors and abilities and difficulty learning or processing new information. As the disease progresses, memory deficits tend to appear. Reported impairments range from short-term memory deficits to long-term memory difficulties, including deficits in episodic (memory of one's life), procedural (memory of the body of how to perform an activity), and working memory.
Reported neuropsychiatric signs are anxiety, depression, a reduced display of emotions, egocentrism, aggression, and compulsive behavior and hallucination and delusion. Other common psychiatric disorders could include obsessive–compulsive disorder, mania, insomnia and bipolar disorder. Difficulties in recognizing other people's negative expressions have also been observed. The prevalence of these symptoms is highly variable between studies, with estimated rates for lifetime prevalence of psychiatric disorders between 33 and 76%. For many with the disease and their families, these symptoms are among the most distressing aspects of the disease, often affecting daily functioning and constituting reason for institutionalization. Early behavioral changes in HD result in an increased risk of suicide. Often, individuals have reduced awareness of chorea, cognitive, and emotional impairments.