Huntington’s Disease

Česká verzia

Authors: doc. Mudr Jan Roth, CSc.
Authors place of work: Univerzita Karlova, Neurologická klinika 1. LF UK a VFN Praha
Published in the journal: Cesk Slov Neurol N 2010; 73/106(2): 107-123
Category: Minimonography

Summary

Huntington’s disease (HD) is an autosomal dominantly inherited neuropsychiatric degenerative condition with a fatal prognosis. It is caused by mutation – the expansion of CAG (containing cytosine-adenine-guanine) triplet repeats 40 and more at the short arm of 4th chromosome. The main clinical features are motor impairment (especially choreatic dyskinesias and the impairment of voluntary movements), progressive cognitive deterioration and personality changes. The product of the mutation is an aberrant protein known as huntingtin with an enlarged polyglutamine stretch. The prevalence of HD is approximately 1 : 10–15,000. The typical onset of HD is in the 4th decade with a minority of cases starting in childhood or adolescence (juvenile HD) or in patients over 65 years of age (late-onset of HD). The initial symptoms are usually non-specific: behavioural changes, personality and affective disorders. As HD progresses, cognitive disturbance appears, leading to severe dementia. Typical motor symptoms are choreatic and/or dystonic dyskinesias, the impairment of voluntary movements, gait disorder, dysfagia and dysarthria. The progression of HD leads inevitably to a marantic, cachectic state and loss of the ability to make voluntary movements, to ingest food, control of urination and defecation, etc. Therapeutic interventions can only target symptoms. The degree of choreatic dyskinesias may be alleviated by antipsychotics, risperidone or tiapride for preference, or by GABAergics (clonazepam) or depletors of dopamine (tetrabenazine). Marked improvement of dystonia may occur with amantadine. In juvenile forms of HD with akinetic syndrome it is possible cautiously to use L-DOPA or amantadine. Irritability and agresivity respond to antipsychotics, sertraline or valproate. Psychotic symptoms may be treated in accord with routine psychiatric protocoles. Adequate (hypercaloric) food intake is extremely important. Sipping or even percutaneous gastrotomy is often indicated in the advanced stages of HD. A multidisciplinary approach (neurology, genetics, psychiatry, speech therapy, physiotherapy and ergotherapy, dietetics, social support etc.) in HD is essential. Genetic testing confirms the clinical diagnosis. Adult and healthy people at risk may be able to request predictive genetical testing, but specific protocolary procedure is realized. Children and adolescents are not tested. Prenatal testing is also available. Pre-implantation genetic diagnosis allows to give the birth of a healthy child without knowing of the genetical state of whichever parent at HD risk.

Key words:
Huntington’s disease – CAG triplet – genetic testing – chorea – dementia

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