Presymptomatic ALS genetic counseling and testing: Experience and recommendations

Abstract

Remarkable advances in our understanding of the genetic contributions to amyotrophic lateral sclerosis (ALS) have sparked discussion and debate about whether clinical genetic testing should routinely be offered to patients with ALS. A related, but distinct, question is whether presymptomatic genetic testing should be offered to family members who may be at risk for developing ALS. Existing guidelines for presymptomatic counseling and testing are mostly based on small number of individuals, clinical judgment, and experience from other neurodegenerative disorders. Over the course of the last 8 years, we have provided testing and 317 genetic counseling sessions (including predecision, pretest, posttest, and ad hoc counseling) to 161 first-degree family members participating in the Pre-Symptomatic Familial ALS Study (Pre-fALS), as well as testing and 75 posttest counseling sessions to 63 individuals with familial ALS. Based on this experience, and the real-world challenges we have had to overcome in the process, we recommend an updated set of guidelines for providing presymptomatic genetic counseling and testing to people at high genetic risk for developing ALS. These recommendations are especially timely and relevant given the growing interest in studying presymptomatic ALS.

Figure.. Presymptomatic genetic counseling in the Pre-Symptomatic Familial ALS Study (Pre-fALS)

As of February 2016, 273 individuals provided consent to participate in Pre-fALS. A total of 48 failed early screening procedures and were excluded; 20 are still in the early stage of screening. Among the 25 known status participants, 5 requested and received ad hoc genetic counseling (due to the absence or inadequacy of prior genetic counseling). A total of 11 participants requested and received predecision counseling to aid their decision of whether to learn genetic test results; over half of them ultimately chose to enroll in the nondisclosure arm of the study. A total of 145 disclosure participants have completed pretest counseling (with 11 participants receiving a second pretest counseling session because of a prolonged delay following the initial pretest counseling session), and all of them have also completed posttest counseling. In total, we have provided 317 counseling sessions to 161 presymptomatic participants, and 113 participants have been enrolled in the Pre-fALS Cohort (with 7 eligible participants excluded due to difficulty scheduling study visits). In addition, we have provided 75 posttest counseling sessions to 63 affected individuals for whom we have performed genetic testing in order to genotype the family, which is a prerequisite for their family members' eligibility for Pre-fALS. A total of 12 of them received an additional counseling session after results of a more recently discovered gene mutation became available.