Huntington disease
What is Huntington disease?
What are the symptoms of Huntington disease?
What causes Huntington disease?
How is Huntington disease diagnosed?
What treatments are available for Huntington disease?
Huntington disease , a relatively rare, and invariably fatal, hereditary neurological disease that is characterized by irregular and involuntary movements of the muscles and progressive loss of cognitive ability. The disease was first described by American physician George Huntington in 1872.
Symptoms and progression
Symptoms of Huntington disease usually appear between ages 35 and 50 and worsen over time. They begin with occasional jerking or writhing movements, called choreiform movements, or what appear to be minor problems with coordination; these movements, which are absent during sleep, worsen over the next few years and progress to random, uncontrollable, and often violent twitchings and jerks. Symptoms of mental deterioration may appear, including apathy, fatigue, irritability, restlessness, or moodiness; these symptoms may progress to memory loss. Neuropsychiatric symptoms often closely resemble those of dementia, bipolar disorder, or schizophrenia.
Cause
Huntington disease is caused by a genetic mutation in a gene known as HTT (officially named huntingtin). A child of someone with the disease has a 50 percent chance of inheriting the mutation, and all individuals who inherit it will eventually develop the disease.
The HTT gene, which is located on human chromosome 4, encodes a protein called huntingtin, which is distributed in certain regions of the brain, as well as other tissues of the body. Mutated forms of HTT contain abnormally repeated segments of deoxyribonucleic acid (DNA) known as CAG trinucleotide repeats. These repeated segments result in the synthesis of huntingtin proteins that contain long stretches of molecules of the amino acid glutamine. When these abnormal huntingtin proteins are cut into fragments during processing by cellular enzymes, molecules of glutamine project out from the ends of the protein fragments, causing the fragments to adhere to other proteins. The resulting protein clumps have the potential to cause neuron (nerve cell) dysfunction. This process leads to the degeneration and eventual death of neurons in the basal ganglia, a pair of nerve clusters deep within the brain that control movement.
The progression and severity of Huntington disease are associated with the length of the CAG trinucleotide repeat region in the HTT gene. For example, the trinucleotide region in HTT appears to expand during middle age, coinciding with the onset of symptoms, and may also expand from one generation to the next, causing a form of the disease known as anticipation, in which symptoms develop at an earlier age in the offspring of affected individuals.
Diagnosis and treatment
Huntington disease is diagnosed through a comprehensive process that includes a neurological exam and thorough evaluation of medical and family history, which can be a major diagnostic clue, owing to the hereditary nature of the disease. Diagnosis is confirmation by genetic testing, which the most accurate approach being a direct genetic test, in which DNA is isolated from a blood sample and analyzed to determine the number of CAG repeats in HTT.
- Also called:
- Huntington’s diseaseor Huntington chorea
- On the Web:
- Patient - Huntington's disease (Dec. 19, 2025)
There is no cure for Huntington disease, and thus treatment focuses on managing symptoms and improving quality of life. For examle, choreiform movements may be partially and temporarily suppressed by phenothiazines or other antipsychotic medications. Antidepressants and other mood stabilizers can help manage symptoms of depression, anxiety, and fluctuations in emotional state. Promising gene-editing and gene therapy approaches targeting the underlying genetic cause are in clinical trials. One such agent is AMT-130, a one-time gene therapy that uses a modified virus to deliver an HTT-targeting microRNA (miRNA) directly to brain cells. The miRNA deactivates HTT, thereby reducing production of the huntingtin protein. Trials have shown that within three years of treatment, a high dose of AMT-130 slows the progression of Huntington disease by 75 percent.
