Huntington's Disease (HD) is a progressive brain disorder caused by a defective gene. This disease causes changes in the central area of the brain, which affect movement, mood and thinking skills.
About Huntington's Disease
Huntington's disease is a progressive brain disorder caused by a single defective gene on chromosome 4 — one of the 23 human chromosomes that carry a person’s entire genetic code.
This defect is "dominant," meaning that anyone who inherits it from a parent with Huntington's will eventually develop the disease. The disorder is named for George Huntington, the physician who first described it in the late 1800s.
The defective gene codes the blueprint for a protein called huntingtin. This protein's normal function isn't yet known, but it's called "huntingtin" because scientists identified its defective form as the cause of Huntington's disease. Defective huntingtin protein leads to brain changes that cause abnormal involuntary movements, a severe decline in thinking and reasoning skills, and irritability, depression and other mood changes.
Symptomsback to top
Symptoms of Huntington's disease usually develop between ages 30 and 50, but they can appear as early as age 2 or as late as 80. The hallmark symptom of Huntington's disease is uncontrolled movement of the arms, legs, head, face and upper body. Huntington's disease also causes a decline in thinking and reasoning skills, including memory, concentration, judgment and ability to plan and organize.
Huntington's disease brain changes lead to alterations in mood, especially depression, anxiety, and uncharacteristic anger and irritability. Another common symptom is obsessive-compulsive behavior, leading a person to repeat the same question or activity over and over.
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Diagnosisback to top
Experts strongly recommend professional genetic counseling both before and after genetic testing for Huntington's disease.
Scientists identified the defective gene that causes Huntington's disease in 1993. A diagnostic genetic test is now available.The test can confirm that the defective gene for huntingtin protein is the cause of symptoms in people with suspected Huntington's disease and can detect the defective gene in people who don't yet have symptoms but are at risk because a parent has Huntington's.
Causes and risksback to top
The defective gene identified in 1993 causes virtually all Huntington’s disease.
The huntingtin gene defect involves extra repeats of one specific chemical code in one small section of chromosome 4. The normal huntingtin gene includes 17 to 20 repetitions of this code among its total of more than 3,100 codes. The defect that causes Huntington's disease includes 40 or more repeats. Genetic tests for Huntington's disease measure the number of repeats present in an individual's huntingtin protein gene.
Scientists don't yet understand the normal function of huntingtin protein or how a few dozen extra repeats in its genetic blueprint lead to the devastating symptoms of Huntington's disease. Researchers are eager to solve these mysteries to find the answer to Huntington's. These solutions also may offer important insights into a wide range of other brain disorders, including Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS). Sign up for our enews to receive updates about Alzheimer’s and dementia care and research.
Help is available
Huntington's Disease Society of America (HDSA) provides information, services and advocacy for people with Huntington's disease and their families. They also have referrals to genetic testing centers. Call HDSA at 800.345.4372.
The Alzheimer's Association can help you learn more about Alzheimer's disease and dementia, and help you find local support services. Call our 24/7 Helpline at 800.272.3900.
National Human Genome Research Institute
Provides information about genetics and Huntington's disease
Treatment and outcomesback to top
There is currently no cure for Huntington's disease and no way to slow or stop the brain changes it causes. Treatments focus on managing symptoms. A group of international experts recommended the following treatments as first-line strategies for three of the disease's most troubling symptoms:
- Chorea (involuntary movements): Some experts believe beginning treatment with an atypical antipsychotic drug, such as olanzapine, is best. Others start with another type of drug recently approved by the U.S. Food and Drug Administration (FDA) specifically for Huntington’s, called tetrabenazine.
- Irritability: For severe anger and threatening behavior, experts agree that an atypical antipsychotic drug is the preferred approach. For less severe, nonthreatening irritability, experts recommend first trying a selective serotonin reuptake inhibitor (SSRI), which is a type of antidepressant.
- Obsessive-compulsive thoughts and actions: Experts also recommend SSRIs as the standard treatment for these symptoms.
Other Huntington's symptoms, such as anxiety, depression and insomnia, also should be treated according to generally accepted guidelines. Experts encourage people with Huntington's to keep all their medical appointments and not to get discouraged if it takes their health care team some time to find the best drugs and the most effective doses.
LOOKING OUTSIDE THE BOX
Juvenile Huntington disease (JHD) is a devastating neurodegenerative disease that is characterized by behavioral, cognitive, and motor decline. While most clinicians learn about Huntington disease during professional training, many may not be aware of its onset during childhood and adolescence. JHD accounts for 5% to 10% of Huntington disease cases.1 Manifestation of the disease before age 21 is considered juvenile onset; childhood onset occurs before age 11.
Few studies have attempted to assess the population-based prevalence of JHD. A 2013 study in the UK found that the average annual prevalence of JHD was 6.77 per million (95% confidence interval, 5.60 to 8.12 per million).2 Whether onset occurs during adolescence or adulthood, behavioral and psychiatric manifestations are very common. Initial symptoms of JHD are often insidious and may appear disparate. This can make it difficult to establish the diagnosis, which is often delayed.3,4
Huntington disease is inherited in an autosomal dominant pattern. The disease is caused by a mutation leading to CAG repeat expansion in the first exon of the HTT gene. It appears that the age of onset of JHD is inversely correlated with the number of CAG repeats.5,6 Paternal inheritance is the mode of transmission in the majority of JHD cases.7 It is important, however, to consider the diagnosis even without a positive family history; cases have been reported in which the father had yet to show symptoms at the time of the evaluation of the child.4
Distinctions between the presentations of JHD and adult Huntington disease are outlined in the Table. The Huntington Study Group developed and validated the Unified Huntington Disease Rating Scale, which was published in 1996.8 The scale includes symptom categorization of all disease domains.
The literature describes several cases in which psychiatric and behavioral symptoms precede the typical motor symptoms.4 Symptoms may also appear to plateau before progressing. Symptom categorizations are used to describe disease progression in JHD: initial behavioral and cognitive changes; subsequent gait disturbance, rigidity of the extremities, and involuntary movements; then a phase of worsening cognitive decline, rigidity, speech regression, and seizures; to an ultimate stage of worsening immobility, hypotonia, dysphagia, and aspiration.9
The psychiatric manifestations of JHD fall into several symptom domains. Psychiatric symptoms include depression, anxiety, irritability, agitation, aggression, inattention, obsessiveness, impulsivity, and apathy. Changes in sleep patterns are also common. As the disease progresses, these symptoms become more impairing and increasingly difficult for family and care providers to manage.
Peter, age 14, is brought to the ED after an episode of severe aggression against his brother. ADHD and anxiety disorder were diagnosed when he was in the first grade. He was a bright child but struggled significantly with staying on task at school and with impulsivity and irritability. At age 11, Peter saw a pediatric neurologist because of concerns about changes in his gait and “spacing out” frequently at school. After further workup, JHD was diagnosed. Genetic testing confirmed the diagnosis and documented 82 CAG repeat expansions of the HTT gene. Huntington disease was later diagnosed in his father.
Peter began to struggle more with academic tasks and self-care, and he had increased difficulty with swallowing. Anxiety worsened, and symptoms of depression emerged. The aggressive episodes became very disruptive both at school and at home. Following inpatient psychiatric care, psychiatric symptoms stabilized and he was able to return home with ongoing outpatient management for a period. He was wheelchair bound within the following year and required 24-hour nursing support at home. Deterioration in behavioral and motor control continued, which made management of these symptoms very difficult for his treatment team.
1. Quarrell O, O’Donovan KL, Bandmann O, Strong M. The prevalence of juvenile Huntington disease: a review of the literature and meta-analysis. PLoS Curr. 2012;4:e4f8606b742ef3.
2. Douglas I, Evans S, Rawlins MD, et al. Juvenile Huntington disease: a population-based study using the General Practice Research Database. BMJ Open. 2013;3:e002085.
3. Chuo YP, Hou PH, Chan CH, et al. Juvenile Huntington disease presenting as difficult to treat seizure and the first episode of psychosis. Gen Hosp Psychiatry. 2012;34:436.e9-11.
4. Ribai P, Nguyen K, Hahn-Barma V, et al. Psychiatric and cognitive difficulties as indicators of juvenile Huntington disease onset in 29 patients. Arch Neurol. 2007;64:813-819.
5. Telenius H, Kremer HPH, Theilmann J, et al. Molecular analysis of juvenile Huntington disease: the major influence on (CAG)n repeat length is the sex of the affected parent. Hum Mol Genet. 1993;2:1535-1540.
6. Cloud LJ, Rosenblatt A, Margolis RL, et al. Seizures in juvenile Huntington disease: frequency and characterization in a multicenter cohort. Mov Disord. 2012;27:1797-1800.
7. Nicolas G, Devys D, Goldenberg A, et al. Juvenile Huntington disease in an 18-month-old boy revealed by global developmental delay and reduced cerebellar volume. Am J Med Genet A. 2011;155:815-818.
8. Huntington Study Group. Unified Huntington Disease Rating Scale: reliability and consistency. Mov Disord. 1996;11:136-142.
9. Gonzalez-Alegre P, Afifi AK. Clinical characteristics of childhood-onset (juvenile) Huntington disease: report of 12 patients and review of the literature. J Child Neurol. 2006;21:223-229.
10. Robertson L, Santini H, O’Donovan KL, et al. Current pharmacological management in juvenile Huntington disease. PLOS Curr. 2012;4:RRN1304.
11. Beale EA, Baile WF, Aaron J. Silence is not golden: communicating with children dying from cancer. J Clin Oncol. 2005;23:3629-3631.
12. Fink KD, Deng P, Torrest A, et al. Developing stem cell therapies for juvenile and adult-onset Huntington’s disease. Regen Med. 2015;10:623-646.
13. Chan AW, Jiang J, Chen Y, et al. Progressive cognitive deficit, motor impairment and striatal pathology in a transgenic Huntington disease monkey model from infancy to adulthood. PLoS One. 2015;10: e0122335.
14. Beglinger LJ, Nopoulos PC, Jorge RE, et al. White matter volume and cognitive dysfunction in early Huntington disease. Cog Behav Neurol. 2005;18:102-107.
15. Patra P, Shirolkar MS. Childhood onset (juvenile) Huntington disease: a rare case report. J Pediatr Neurosci. 2015;10:276-279.