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Huntington’s disease (HD) is progressive neurodegenerative disorder. The prevalence in Europe is 5-10 per 100.000. Typical symptoms include irresistible hyperkinetic movements of the limbs and the muscles of trunk and head. In most cases there is a cognitive decline, yet the amplitude of which is quite variable. Psychiatric symptoms are common and may as well be very variable (depression, schizophrenia and others). On the morphological level there is a selective death of certain neurons, especially within the basal ganglia (caudate nucleus) and the cortex.
HD is a disorder with usually adult onset. Symptoms present between 35 and 45 years of age in most cases. However, patients with earlier as well as much later onset have been described. Juvenile cases are very rare and are often associated with a phenotype different from the adult form of the disease (e.g. Westphal variant).
HD is inherited in an autosomal dominant manner, i.e. virtually all patients carry one normal and one mutated allele. The risk of offspring of a patient to inherit the mutated allele and develop symptoms of HD is 50%, independent of gender. The disease causing gene in HD (huntingtin) has been mapped to chromosome 4p. The mutation consists of an abnormal expansion of a variable trinucleotide repeat (CAG)n within the first exon of the gene. The (CAG)n is translated into an extended polyglutamine stretch within the mature huntingtin protein. Normal alleles comprise up to 35 CAGs, whereas alleles with 36 or more CAGs will cause symptoms of HD. For the alleles between 36 and 40 CAGs reduced penetrance has been described, i.e. some mutation carriers do not develop symptoms of HD even late in their lives. Alleles between 27 and 35 CAGs are not associated with HD symptoms but have a higher risk of further expansion into the pathological range in later generations.Due to the identification of the disease causing mutation nowadays predictive testing for persons at risk for HD is available. Such testing may be only conducted provided that the counselee is attended to by detailed genetic counselling and psychological support. This is in accordance with the recommendations published by the German HD self-support community and the International Huntington Association. Presymptomatic tests in persons before 18 years are generally rejected. Prenatal tests are available but require even more profound support for the counselee by the human geneticists and psychologist.
Dr. med. S. Wieczorek
Humangenetik
Gebäude MA 5
Ruhr-Universität
Universitätsstr. 150
44801 Bochum
GermanyTel.: +49 234 32 23831
Fax: +49 234 32 14196
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