Attitudes of female carriers of X-linked hypohidrotic ectodermal dysplasia towards prenatal treatment and their decisions during a pregnancy with a male fetus

Background: X-linked hypohidrotic ectodermal dysplasia (XLHED) is a severe genetic disorder that may be treatable with short-term protein replacement therapy during fetal development. This is currently being investigated in a multicenter clinical trial. Affected fetuses can be identified by the number of tooth germs during a routine ultrasound scan in mid-gestation. To understand the attitudes of female XLHED carriers towards prenatal treatment and ultrasonographic screening of the fetus, we analyzed an earlier and a very recent survey among those women and the actual decisions of potential trial participants. Methods: Initial analyses were based on a self-administered survey of 167 female XLHED carriers conducted in 2011. A similar questionnaire was completed 12 years later by 72 female XLHED carriers aged 18–45 years. Subsequently, both the path to diagnosis and further decision-making of the first 33 pregnant women screened for participation in the EDELIFE trial were investigated. Results: Most women diagnosed with XLHED considered this disease as an obstacle to having children: About one third had decided not to have children, another third would monitor their pregnancy using invasive genetic testing. In both surveys, a small number of women stated that they would consider termination of pregnancy depending on the test result. When it came to participating in the clinical trial, 80% were likely to take part (17% moderately likely, 63% very likely). Among the first pregnant women screened for this trial, 48% underwent invasive tests, while 52% relied on non-invasive tooth germ imaging for fetal XLHED diagnosis. One pregnancy with an affected fetus was terminated, another one resulted in a miscarriage, one woman declined to participate in the trial, and 12 women (80%) decided to have the affected fetuses treated. Conclusion: Ultrasound-based screening and prenatal treatment of the fetus are viewed positively by the vast majority of female XLHED carriers.