Predictive testing: what it involves: more detail

Which protocol applies?

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 adult onset conditions: a multidisciplinary approach supporting autonomous decision making, neurological and psychiatric evaluation, a two part pre-test counselling process, one or more disclosure sessions conducted in person, and a support person chosen by the patient who attends all visits. Those guidelines allow counselling in person or by videoconference, and they do not address prion disease.

A 2022 review of the genetics of human prion diseases states that genetic counselling in prion disease should follow the Huntington disease protocol, with counselling and neurological and psychiatric examination before testing and repeated afterwards, disclosure with a support person present, and no testing of minors unless there is valid concern that the person may already be symptomatic. It accepts modified protocols, including telemedicine, where specialists are scarce.

The 2026 Israeli practice framework is the first consensus document written for relatives of people with CJD. Its four steps are an initial genetic counselling session, a psychological assessment, a testing appointment for the blood sample, and a results session, with no less than one month from counselling to sampling. Counselling may be delivered 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, ending in written confirmation of readiness; the panel did not reach consensus on whether it may be deferred for someone who declines it. Where there is acute distress the recommendation is to encourage a delay of around six months. Special circumstances, including an ongoing pregnancy, may justify an expedited timeline provided all four steps are preserved.

How are results handled?

The Israeli framework states that all results, positive or negative, should be disclosed in person to the tested individual, by the clinician who gave the initial counselling, and that results return only to that team. Telehealth is not usually recommended for disclosure. 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.

The French experience published in 2019 describes a similar pattern: sequencing on two independent blood samples, with the result given at a dedicated consultation about a month later.

What is the laboratory process?

In the United States, the National Prion Disease Pathology Surveillance Center asks for two 5 mL EDTA tubes shipped at room temperature, Monday to Thursday, states a turnaround of 15 business days from receipt with no STAT option, requires a genetic consent form and a completed social and family history section, and does not test patients under 18. Its listed charge under CPT 81404 is USD 274.83, which the page states applies, effective 1 August 2011, when blood is submitted for a patient without a confirmed family history of genetic CJD.

In Australia, the national CJD registry states that genetic testing is entirely voluntary, that PRNP testing 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 published. The page recommends storing DNA from every suspected case so that relatives can consider testing later.

What can and cannot be concluded from a result?

A result establishes carrier status for a known variant. It does not establish age at onset, and for several variants it does not establish that illness will occur. The 2022 review describes D178N and P102L as nearly completely penetrant, E200K as incompletely and age-dependently penetrant, and V180I and V210I as low penetrance at roughly 1 percent and 10 percent, with penetrance for octapeptide repeat insertions generally increasing with repeat number. An international study of 217 E200K carriers did not confirm anticipation.

Codon 129 modifies phenotype rather than carrier status, most strikingly for D178N: 129M in cis with the variant usually produces fatal familial insomnia, 129V in cis usually produces genetic CJD.

The figure usually quoted for inheritance is 50 percent per child. A 2025 study of 24 Spanish pedigrees reported higher transmission for D178N and E200K and argued for variant-specific and sex-specific figures; it is retrospective, partly based on inferred genotypes and weighted towards Basque families. Both positions are worth having ready when a family asks why they have seen different numbers. What a result can tell you is the plain page on this.

What does the published outcome data show?

It is thin, and it does not support the assumption that knowing is easier than not knowing. In the French series, 30 at-risk relatives attended between 2004 and 2017; 20 proceeded to testing, 8 of them carrying the family variant, and 10 chose not to test. At follow up in 2017, with 19 of the 30 taking part, anxiety above threshold was common and similar among non-carriers and untested people, and the authors concluded that deciding in favour of testing did not relieve anxiety about the family disease. Non-carriers described relief at the result alongside continuing concern for relatives. Only three carriers took part, so no comparison can be drawn for that group. The practical implication is that follow up should be offered after every outcome: a positive result, a negative result and a decision not to test.

Minors

Both the prion-specific framework and the general position statements point the same way. The 2026 framework states that testing should not be offered under 18 and that young adults should be carefully considered. The National Society of Genetic Counselors position statement, revised on 16 October 2025, generally discourages predictive genetic testing of asymptomatic minors for adult-onset conditions and predispositions, while allowing that there are circumstances in which testing a minor may be appropriate, and strongly recommends pre-test and post-test genetic counselling.

Reproductive testing in the same conversation

A 2014 JAMA Neurology case report described IVF with preimplantation genetic diagnosis in a woman carrying PRNP F198S, presenting 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 its availability may affect their inclinations for predictive testing and for non-disclosure protocols, in which the person remains unaware of their own genotype.

The 2026 framework distinguishes direct testing of 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 leaving the parent’s status unknown. Exclusion testing is offered there at tertiary centres to first- and second-degree relatives, and such testing is publicly funded for up to two healthy offspring.

Insurance as a factor in timing

In the United Kingdom, the voluntary Code on Genetic Testing and Insurance governs what insurers may ask. The government’s 2025 three-year review states that insurers will never require or pressure any applicant to undertake a predictive or diagnostic genetic test, that Huntington’s disease remains the only exempt illness, and that the exemption applies to life insurance applications above 500,000 pounds. The review also states that the government has not received an application from insurers to add further conditions to that list in over 20 years, and reports that it has heard anecdotally that some people are delaying predictive tests because of concerns about insurance, with systematic evidence yet to be gathered.

Rules differ by country and by product, so this is a question for the counselling appointment and, where needed, for independent advice. Insurance and work covers what is published.

Related pages

Predictive testing is the plain version. Genetic counselling comes first covers the pathway, and the right not to know the decision to decline.

This page describes published practice and literature. It is not clinical, genetic, legal or insurance advice, and it is not a recommendation for or against testing.