Genetic counselling comes first: more detail

Which protocols are in use?

The 2011 joint practice guidelines of the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors, written for Alzheimer disease, describe the Huntington Disease Society of America protocol as the gold standard for genetic testing in adult onset conditions. Its elements are a multidisciplinary approach aimed at autonomous decision making, a neurological examination, a psychiatric evaluation, a two part pre-test counselling process and one or more disclosure sessions held in person, with a support person chosen by the patient attending all visits. That document does not address prion disease.

A 2022 review of the genetics of human prion diseases from the Case Western Reserve prion group states that genetic counselling in this setting should follow the Huntington disease protocol, with counselling plus neurological and psychiatric examination before testing and the same assessments repeated afterwards, disclosure with a support person present, and no testing of minors unless there is a valid concern that the person may already be symptomatic. It allows for a modified protocol, including telemedicine, where specialists are scarce.

What does the 2026 Israeli framework add?

It is the first consensus document built around relatives of people with CJD rather than adapted from another disease. A panel of neurologists, medical geneticists, genetic counsellors, genetics researchers, a cognitive neurology nurse and a medical psychologist from six centres worked through a questionnaire, small working groups, moderated discussion and a vote on unresolved items. A family representative revised the draft to reflect carriers’ views before outside prion experts reviewed it.

The framework sets four steps for an asymptomatic relative: an initial genetic counselling session, a psychological assessment, a separate appointment for blood sampling, and a results session. The interval from counselling to sampling should be no less than one month. Special circumstances, an ongoing pregnancy among them, may justify an expedited timeline, while preserving all four steps. Counselling may be given by a medical geneticist, a genetic counsellor or a neurologist familiar with the disease. The psychological assessment is a structured in person evaluation by an experienced mental health professional, concluding in written confirmation of readiness; the panel did not reach consensus on whether it can be deferred when someone declines it. Where there is acute distress, the recommendation is to encourage delay, by around six months.

All results, positive or negative, are to be disclosed in person, by the clinician who gave the initial counselling, with results returning only to that team. Telehealth is not usually recommended for disclosure. Testing is not to be offered below age 18, and young adults are to be considered carefully. For E200K the framework describes targeted Sanger sequencing with a local positive control in a certified genetics laboratory, with full PRNP coding sequencing by gene panel or exome in selected cases.

Two of its judgements are worth noting for other countries. The panel considered it impractical to advocate testing on the basis of family origin alone, because that could stigmatise communities in which the absolute risk is low, and genetic CJD is not part of Israel’s routine carrier screening. The panel also recommends that counselling and testing be publicly funded, and notes that a structured support programme for carriers is not currently available in the country.

What is known about outcomes?

The published series are small. A French clinic at Pitie-Salpetriere reported 30 at-risk relatives seen between 2004 and 2017 under a protocol involving geneticists, psychologists and genetic counsellors, with PRNP sequencing on two independent blood samples and results given at a dedicated consultation about a month later. Twenty chose to be tested, of whom eight carried the family variant and twelve did not; ten chose not to be tested. In the 2017 follow up, which 19 of the 30 joined, anxiety scores above threshold were common and similar in non-carriers and in untested people, and the authors concluded that deciding in favour of testing did not relieve anxiety about the family disease. Only three carriers took part, so the study draws no firm comparison for that group.

That finding has a practical consequence for counselling: support is worth offering on both sides of the decision, and the absence of a result is not the absence of a burden.

What penetrance information should counselling cover?

The 2022 review states that genetic prion diseases were once thought fully penetrant and are now recognised to have variable penetrance. It describes E200K as showing incomplete, age-associated penetrance, gives V180I as about 1 percent penetrant and V210I as about 10 percent, and describes D178N and P102L as nearly completely penetrant. Figures of this kind come from population databases and surveillance series and continue to be revised, so a counsellor working with a particular family will want the current literature for that variant.

Transmission itself has also been questioned. A 2025 study of 24 Spanish pedigrees reported inheritance above the expected 50 percent for two variants, with meiotic drive proposed as the most plausible explanation. Those authors argue for variant-specific and sex-specific figures in counselling. The study is retrospective, 18 percent of genotypes were inferred rather than tested, and the sample is weighted towards Basque families, so the 50 percent figure remains the one in current guidance documents. Genetics and family risk covers how this is put to families.

Where is testing done, and what does it cost?

Arrangements differ by country, and the practical details change how a consultation runs.

In the United States, the National Prion Disease Pathology Surveillance Center accepts two 5 mL EDTA tubes shipped at room temperature, with a stated turnaround of 15 business days from receipt and no STAT option. Its request form includes a social and family history section, a genetic consent form is required, and testing is not performed on patients under 18. The listed charge under CPT 81404 is USD 274.83, stated as applying, effective 1 August 2011, when blood is submitted for a patient without a confirmed family history of genetic CJD.

In Australia, the national registry page states that genetic testing is entirely voluntary, that the PRNP test is run by the Neurogenetics Unit of PathWest Laboratory Medicine in Nedlands on peripheral blood or unfixed autopsy brain tissue, and that consultation with a genetic service is recommended. No price or turnaround is listed. The page also recommends storing DNA from every suspected case so that relatives can consider testing later, which is a point worth raising with a family during the illness rather than after it.

Commercial laboratories reach at-risk people directly in some countries. A German laboratory offers a predictive dementia panel of nine genes including PRNP, and states that comprehensive counselling with a specialist in human genetics and a declaration of consent after the consultation, if necessary after a reflection period, are absolute prerequisites.

What about reproductive options?

A 2014 JAMA Neurology case report from Duke University, two Chicago reproductive medicine centres, the University of Chicago and the UCSF Memory and Aging Center reported IVF with preimplantation genetic diagnosis in a woman with PRNP F198S, which causes Gerstmann-Straussler-Scheinker syndrome, and described itself as the first published report of the approach in a genetic prion disease with 27 month follow up of the children. The authors concluded that clinicians should discuss preimplantation genetic diagnosis as an option with patients genetically predisposed to prion disease, and that it may affect their inclinations for predictive testing. Non-disclosure protocols, in which the at-risk person remains unaware of their own genotype, were discussed with that patient as an option; she chose to learn her status.

The 2026 Israeli framework separates direct preimplantation genetic testing, which tests embryos for a known family variant, from exclusion testing, which selects embryos that did not inherit the at-risk allele from the affected grandparent while the parent’s own status stays unknown. Exclusion testing is offered at tertiary centres there to first- and second-degree relatives, and such testing is publicly funded for up to two healthy offspring. Family planning options covers this in plainer words.

Related pages

Genetic counselling comes first is the plain version of this page. Finding a counsellor lists the routes to a service. Predictive testing and what a result can tell you cover the test and the result.

This page describes published practice. It is not clinical, genetic, legal or insurance advice for any individual.