Lessons learned from 30 years of presymptomatic testing in Huntington Disease

Presymptomatic testing allows individuals to undergo genetic testing for inherited diseases before symptoms manifest. While valuable in conditions with available preventive strategies, no therapeutic prevention currently exists for Huntington disease, making testing a personal choice rather than a medical recommendation. Available in France since 1992 - following the identification of CAG repeat expansions (>35) in the huntingtin gene - presymptomatic testing is governed by guidelines emphasizing autonomy, benevolence, informed consent, confidentiality, and equity. Its implementation requires an interdisciplinary approach, including genetic counseling and psychological support, to ensure comprehensive care. One of the many lessons learned is that despite the large availability of presymptomatic testing centers, less than 20% of at-risk individuals choose to be tested, reflecting complex psychological and familial dynamics. In addition, motivations for testing vary widely, more often identified as the desire to know rather than family planning, which explains the even lower opting in for prenatal testing. Psychological support is essential, as an unfavorable result puts individuals in a prolonged liminal state, waiting for disease onset. Favorable results are the happy ending of testing, but can, in some instances, also trigger complex emotional responses, such as survivor's guilt. Involving presymptomatic carriers in research programs has offered important scientific benefits and also a sense of agency and meaning for participants. Our experience with presymptomatic testing in Huntington disease has established a paradigm for predictive genetic medicine, highlighting the importance of interdisciplinary care and ethical considerations. As genomic medicine advances, the core principles of presymptomatic testing remain relevant, ensuring the protection and consent of individuals and their families. These lessons help to disseminate information about the utility of genetic counseling and call for an informed approach to presymptomatic testing in neurogenetics.