Huntington disease (Huntington chorea) is a hereditary disorder characterized by progressive motor, cognitive and behavioral impairment.
Huntington disease is a progressive neurodegenerative disorder with an autosomal dominant inheritance pattern characterized by the loss of the neurons in the cortex and basal ganglia of the brain. These lesions, in turn, cause the development of dementia, involuntary movements, and some behavioral disturbances. The average disease prevalence is approximately 2.7 per 100.000 with lower incidence in Asia and higher in Australia.
The disorder is caused by a cytosine-adenine-gyanine (CAG) polyglutamine repeat expansion in the Huntington gene located on chromosome 4. This gene is known to control the production of the protein huntingtin. Interestingly, the age of onset correlates with the length of the CAG repeat – the longer is the repeated region the earlier manifests the disease. Less than 28 repeats is considered normal. Those who have from 28 to 35 repeats in the gene won’t develop the disease but the future generations may be at risk. Individuals who have from 36 to 39 repeats of the CAG sequence may develop the disease at some point, but usually in the advanced age. The presence of more than 40 repeats in the gene indicates that a person will develop the disease for sure – the age of onset reversibly correlates with the CAG repeats quantity, meaning that the more repeats a person has the earlier he/she will experience the first symptoms.
The gene is inherited in an autosomal-dominant pattern meaning that if one of the person’s parents has an abnormal gene a person will inherit it and can develop the disease.
Individuals with an increased number of repeats in the Huntington gene eventually loss the neurons located in the basal ganglia, namely, the caudate nucleus and putamen and the brain cortex with subtle changes in other regions of the brain.
The classic triad characteristic for HD includes motor impairment, cognitive decline, and behavioral changes. The disease usually manifests at one’s 40ies, though sometimes it can become apparent already in small kids. HD developing before a person reaches his/her 20ies is referred to as juvenile Huntington’s disease. Rarely the disease onset takes place after the age of 60 years.
- Motor signs – chorea, abnormal brief, irregular involuntary non repetitive movements, is a typical symptom of Huntington disease. As the disorder progresses chorea may, at last, be substituted by some Parkinson’s-like features such as slow movements, rigidity, and postural instability. Another usual sign of HD is the abnormal eye movement.
- Cognitive retardation is probably the most dramatic symptom of Huntington’s disease. Affected individuals are unable to make decisions, cannot switch easily from one activity to another. Even more, they are unaware of their disease, movement disorders, and psychologic issues.
- Behavioral changes develop depression (almost half of those who suffer from Huntington disease experience symptoms of depression at some point), paranoia, psychosis, obsessive-compulsive symptoms, sexual and sleep disorders, and changes in personality are also common in individuals with Huntington disease.
Huntington disease is also associated with weight loss and cachexia.
- Genetic testing can confirm the presence of an abnormal quantity of the CAG repeats in the Huntington gene;
- PET/MRI scan will reveal brain atrophy and changes in the caudate.
The disease is incurable. Some medications may be given for symptomatic relief and to improve a person’s quality of life.
It was reported that involuntary movements may be induced by stress and anxiety, therefore, the organization of a relaxing and calm environment may be helpful. If these measures are not effective, tetrabenazine or deutetrabenazine are prescribed. Antipsychotics are used to reduce the psychiatric symptoms and also influence on chorea. Atypical neuroleptics (olanzepine, risperidone, etc.), as well as typical neuroleptics (haloperidol), are administered.