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Clinical Symptomatology of Huntington’s Disease

  • Jan Roth
Chapter

Abstract

Huntington’s disease (HD) is a dominantly inherited autosomal neuropsychiatric degenerative disease with a fatal prognosis, caused by a mutation—the expansion of C-A-G (cytosine-adenine-guanine) triplet repeats 40 and more repetitions on the short arm of fourth chromosome. The product of the mutation is an aberrant protein called huntingtin with an enlarged polyglutamine stretch. The prevalence of HD is approx. 1:10–15,000. The typical onset of HD is in the fourth decade, with a minority of cases starting in childhood or adolescence (juvenile HD) or in patients older than 65 years of age (late onset HD).

Early symptoms of classical form are usually nonspecific: behavioral changes, personality disorders, affective symptoms, etc. The affected person begins to be apathetic, emotionally flattened, losing interest in any hobbies. Other patients show jealousy, paranoid suspicions, obsessive thoughts, and compulsive acts. The patients have difficulties with work-related activities, partly due to the early appearance of executive dysfunction, and partly due to apathy and lack of concern. Typical motor symptoms are choreatic and/or dystonic dyskinesias, the impairment of voluntary movements, gait disorder, dysphagia, and dysarthria.

In the progression of HD cognitive disturbance appears leading to severe dementia. During the course of the disease, chorea is individually progressive, eventually decreasing in intensity, spontaneously subsiding and converting to dystonia, and finally to akinesia. The progression of HD leads inevitably to the marantic, cachectic state with a total loss of voluntary movement.

The first signs in juvenile form are difficulties with school activities related to psychomotor retardation, motor dyscoordination, voluntary movement impairment, and cognitive deterioration. Behavioral changes are characteristic for JHD: outbursts of anger, aggression, antisocial tendencies as well as obsessive thoughts and compulsive acts. Psychotic manifestations are more common than in adults with HD. Chorea is rare, dystonia and/or rigidity with akinesia dominate. Gait disorder with postural instability and frequent falls arises rapidly. Myoclonus of the head and trunk, postural and kinetic tremor of the upper extremities as well as supranuclear gaze palsy are frequently present. Epileptic seizures could be present.

Late onset form has a relatively benign course and most patients live to the average age of the healthy population. The principal and incipient manifestation is chorea, whose distribution and character do not differ from the classical form of the disease, but is less intensive and progresses more slowly. Apathy, depression, and irritability are frequent behavioral manifestations. Isolated cognitive deficits are usually present (especially dysexecutive syndrome and short-term memory impairments), but to the lesser degree than in the classical form. Severe dementia does not usually develop.

Clinical diagnosis is confirmed using a genetic test. Adult and healthy people at risk could ask for the predictive genetical testing, but a specific protocol is needed. Children and adolescents are typically not tested. Prenatal testing is also available. A preimplantation genetic diagnosis can determine the health of the embryo without knowing the genetic risk factors of the parents.

Keywords

Huntington’s disease CAG triplet Chorea Dementia Behavior 

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Jan Roth
    • 1
  1. 1.Department of Neurology and Center of Clinical Neuroscience, First Faculty of MedicineCharles University and General University Hospital in PraguePragueCzech Republic

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