DNA analysis of Huntington's disease - Five years of experience in Germany, Austria, and Switzerland

Objective: To review the direct DNA testing for Huntington's disease (HD) i n Germany, Switzerland, and Austria from 1993 to 1997, and to analyze the p opulation with regard to age structure, gender, and family history. Methods : Twelve laboratories (nine in Germany, two in Austria, and one in Switzerl and) recorded data pertaining to repeat number, gender, age at molecular di agnosis, and family history of probands. The molecular test was categorized as either diagnostic (for symptomatic individuals), presymptomatic (for in dividuals at risk), and prenatal (for pregnancies at risk). Results: A tota l of 3,090 HD patients, 992 individuals at risk, and 24 fetuses were invest igated using DNA analysis. The clinical diagnosis was confirmed in 65.6% of patients. A total of 38.5% of individuals at risk inherited an expanded CA G repeat. The female-to-male ratio showed a distinct predominance of women both in the diagnostic and presymptomatic groups. Of the fetuses tested, si x were carriers of an expanded CAG repeat. Two pregnancies were interrupted ; one pregnancy was not. No information about the parents' decision was obt ained for the remaining three pregnancies. Conclusions: Approximately 20% o f the estimated 10,000 HD patients living in Germany, Switzerland, and Aust ria have been identified by DNA analysis (total population, approximately 1 00 million; incidence of HD, 1:10,000). Assuming a ratio of HD patients to individuals at risk of 1:3, approximately 30,000 individuals are, in princi ple, eligible for a presymptomatic test. Less than 3 to 4% of individuals a t risk have requested a presymptomatic test. This shows that the assumed en ormous request of predictive testing has not occurred. More surprisingly, p renatal diagnoses were found to be rare.