Choices couples make in prenatal testing for Huntington’s disease
Huntington’s disease (HD) is an autosomal dominant, adult onset, progressive neurodegenerative disorder of movement, cognition and behaviour affecting ~1 in 10,000 individuals. Prenatal testing for HD is available by two approaches. The direct gene test detects the presence or absence of the expanded CAG-repeat, but may reveal information about the disease status of an at-risk parent. In exclusion testing, the affected grandparental chromosome is excluded by linkage analysis and the 50% risk of the at-risk parent is preserved. If the affected grandparental locus cannot be excluded, the fetus would share the same 50% risk as their at-risk parent.
We have performed a total of 35 prenatal diagnoses in 19 couples in the years 1989-2005. Of these, 11 exclusion tests (32%) were performed in 7 couples and 24 direct gene tests (69%) were performed in 13 couples. In our service, the uptake of exclusion testing has been continually reducing since the introduction of the direct gene test. The experience from a Canadian study revealed no exclusion tests were performed since the direct test became available. This is contrary to a UK study (49%) and a Netherlands study (43%) which showed exclusion testing in 40-50% of prenatal tests.
In our experience, the proportion of exclusion vs. direct tests has shown a considerable decrease since the direct test became available in 1993. One explanation for this observation may be that exclusion testing has become less acceptable now that highly accurate direct testing is available. Ethical reservations may also be raised by the termination of a fetus at 50% risk. Furthermore, parents, after having used exclusion testing and staying asymptomatic at old age could discover that termination of a fetus at 50% risk had been unnecessary, or alternatively, the disease status of a child with the high risk chromosome would be known as soon as the at-risk parent develops symptoms.