Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Huntington's Disease [G10]

OMIM numbers: 143100613004 (HTT) 

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh, Dr. med. Imma Rost

Scientific Background

The prevalence of Huntington's disease, an autosomal dominant neurodegenerative disease, is 5-7 in 100,000 in Central Europe. The average age of onset is 40 years; children and elderly patients are rarely affected. The signs and symptoms mainly include movement disorders which become choreatic with time, changes of the personality, ranging from frequent depressive mood and mental degradation in the beginning to dementia due to atrophy of the caudate nucleus and the putamen or the cortex. Duration of the sickness is 15 years on average.

The disease is caused by a CAG triplet-repeat expansion in exon 1 of the HTT gene. Healthy persons carry alleles with 6-26 CAG repeats; from 40 repeats and above, Huntington's disease occurs with full penetrance. There is a certain statistic correlation between repeat length and the age of onset. Due to CAG repeat expansion, glutamine residues are increasingly integrated into the Huntington protein. The mechanism leading to atrophy of certain brain regions is not fully understood yet. There is no causal therapy; movement disorders and psychological changes can be treated symptomatically.

Generally genetic diagnostic testing is performed to confirm a suspected diagnosis in a patient with clinical signs and symptoms of a certain genetic disease. In predictive genetic testing, at-risk, asymptomatic individuals are tested, usually first-degree relatives of affected patients. According to the Genetic Diagnosis Act (GenDG) genetic counseling should be offered along with any genetic diagnostic procedure. In the case of predictive genetic testing, genetic counseling must be carried out prior to testing as well as after having received the result, unless there exists a written waiver of the at-risk person after having received written information on the content of the counseling. According to the recommendations of medical societies genetic testing should be accompanied by psychotherapeutic counseling prior to, during and after the genetic diagnostic procedure.