A Practice Framework for Genetic Testing in Asymptomatic Relatives of Patients With Creutzfeldt-Jakob Disease:...

Genetic Creutzfeldt-Jakob Disease (gCJD) is an autosomal dominant prion disease caused by heterozygous pathogenic variants in the PRNP gene. It is relatively prevalent in Israel due to a large cluster of individuals from Libyan Jewish origin harboring the p.Glu200Lys variant. In our experience, increasing awareness, expanded reproductive options, and the emergence of research initiatives have led more asymptomatic relatives to seek presymptomatic testing. Since gCJD is a highly penetrant and fatal condition, the decision to pursue testing involves complex medical, psychological, ethical, and familial considerations.

An Israeli multidisciplinary expert panel, familiar with gCJD, collaborated to formulate a structured approach to the genetic testing process of at-risk individuals.

We describe the core components of the recommended presymptomatic testing process, in a real-world setting. We focus on referral considerations, eligibility and timing of testing, psychological assessment, a stepwise approach for the testing process, results disclosure, post-result support, and implications for family planning.

Based on the valuable experience of professionals who address these issues in clinical practice, the proposed framework aims to provide a comprehensive structured methodology for clinicians and care teams supporting individuals at risk for gCJD. It may serve as a model for the testing process of other late-onset monogenic neurodegenerative diseases, in Israel and worldwide.