The Generative Brain

Shir D et al. A practice framework for genetic testing in asymptomatic relatives of patients with Creutzfeldt-Jakob disease, experience and insights from Israel (Eur J Neurol 2026;33(6):e70649, PMID 42333775, PMC13287960)

An open access consensus paper from Israel, published in the European Journal of Neurology in June 2026, that sets out how clinics there handle requests for presymptomatic PRNP testing from healthy relatives of people with genetic CJD, mostly the E200K variant common among Jews of Libyan and Tunisian origin. A panel of 23 professionals from six centres, led from the Neurological Institute of Tel Aviv Sourasky Medical Center with genetics institutes at Hadassah, Sheba, Rambam, Rabin, Wolfson and Meir, met from January to July 2025 and agreed ten recommendations. They cover referral, eligibility and age, reproductive options, psychological appraisal, a four-step testing timeline, the laboratory test, in-person disclosure, support after results and research participation. The authors describe the demand driving it: presymptomatic tests at Tel Aviv rose from two or three a year in 2014 to 2017 to 29 people in 2024. This entry describes the paper for information only; it is not advice to any reader about whether or how to be tested.

Key facts

  • The panel had 23 members (8 neurologists, 5 medical geneticists, 5 genetic counselors, 3 genetics researchers, a cognitive neurology nurse and a medical psychologist) from six centres; it worked through a questionnaire, small working groups, moderated discussion and a vote on unresolved items, and a family representative revised the draft to reflect carriers' views before outside prion experts reviewed it; 29 people are listed as authors.
  • The authors report that presymptomatic testing requests at Tel Aviv Medical Center ran at 2 to 3 a year in 2014 to 2017, rose from 2018, and reached 29 people in 2024, the highest on record; they link the rise to recent diagnoses in relatives, reproductive planning, research advances and the prospect of treatment trials.
  • They estimate that asymptomatic E200K carriers in Israel number in the hundreds to thousands, with penetrance near complete by the ninth decade and mean onset in the early 60s; the youngest known E200K patient was 34 (cited as unpublished data).
  • The panel judged it impractical to proactively offer testing on the basis of family origin alone, because it could stigmatise communities with a low absolute risk; gCJD is not part of Israel's routine carrier screening.
  • The paper states that testing is not offered under age 18, citing the Israeli Genetic Information Law; young adults (about 18 to 25) are to be assessed carefully; and people in acute distress after a relative's diagnosis or death are encouraged to wait at least six months.
  • The process has four steps: genetic counseling, a psychological assessment with a psychiatrist or clinical psychologist ending in written confirmation of readiness, a blood sampling appointment at least one month after counseling, and a results session; pregnancy can shorten the timeline but not remove steps.
  • The panel did not reach consensus on what to do when a person declines the psychological assessment; it framed assessment as a safeguard and cited a Huntington disease review that found only transient distress after testing.
  • For E200K the paper describes targeted Sanger sequencing with a local positive control in a certified genetics laboratory, with full PRNP coding sequencing (gene panel or exome) in selected cases; results go only to the team that gave pre-test counseling, and counseling and testing should be publicly funded, for example by the HMOs.
  • Results, positive or negative, are to be disclosed in person, ideally by the counseling clinician, with a written summary; positive results come with information on age-related penetrance, testing of relatives, reproductive options, support networks and research participation.
  • The paper reports that preimplantation genetic testing is publicly funded in Israel for up to two healthy children, including exclusion PGT for first- and second-degree relatives who do not want to learn their own status, and recommends case by case decisions on PGT and prenatal diagnosis.
  • It states that Israel has no structured support programme for gCJD carriers and calls on health systems and policymakers to build one (Recommendation 9), and recommends offering research participation such as the Tel Aviv natural history study (Recommendation 10).
  • The authors declare no funding and no conflicts of interest; the paper is CC BY-NC-ND licensed and Europe PMC showed no citing papers as of 2026-10-17.

Timeline

  1. 2025Expert panel of 23 professionals from six centres convenes.
  2. 2025Concluding online meeting; all co-authors approve the document.
  3. 2026Manuscript received by the European Journal of Neurology.
  4. 2026Revised version received.
  5. 2026Accepted.
  6. 2026Published online (Europe PMC lists the issue date as June 2026).
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