Talking with families about prion disease

Terminology to use

Goldman and Vallabh (Genetics in Medicine 2022) argue that the term genetic prion disease may now serve providers better than the historical subtype names Creutzfeldt-Jakob disease, fatal familial insomnia and Gerstmann-Straussler-Scheinker disease, because the traditional genotype to phenotype correlation has weakened over time. Variants historically tied to one label do not reliably produce it.

That has a practical consequence. A family told their variant causes fatal familial insomnia may expect insomnia to be the defining feature, and may discount other presentations in relatives, or in themselves. Naming the variant and describing the range is more accurate than naming the syndrome.

Three answers worth having ready

Families ask the same questions, and the guidance answers them clearly.

Will it start at the same age it started in my parent? No. Goldman and Vallabh state that an individual’s age at onset does not appear to be predicted by their affected parent’s age at onset, which differs from Huntington disease and surprises families who have assumed otherwise. If they test positive, their age at onset and presentation could differ from other family members.

Did something bring it on? No known trigger. The guidance states there is no evidence to support an environmental, behavioural or medical trigger for onset of genetic prion disease. Families commonly theorise a recent stressful event or a medical procedure, and where extensive family history exists, variability in age at onset is itself a source of confusion.

Is it starting earlier each generation? There is a lack of anticipation or systematic trend toward earlier onset in later generations. The guidance adds a specific instruction about this one: unless the family raises it, introducing the concept of anticipation, even to explain that it does not apply, is likely to cause only undue distress. That is one of the few places in the literature where counsellors are told not to volunteer accurate information, and the reasoning is sound.

Describing the course

Goldman and Vallabh divide genetic prion disease into rapidly progressive, typically first symptoms to death in under 3 years, and slowly progressive, averaging 3 or more years in total duration. Roughly two-thirds of cases are rapidly progressive, including those caused by the relatively common E200K and D178N variants.

Codon 129 genotype influences duration in some genetic prion disease, and risk in sporadic and iatrogenic disease, but does not appear to influence age at onset for the commonest genotypes in genetic prion disease, though it may in rare cases. Keeping those two apart is worth the effort, because families often collapse them into a single idea of severity.

Penetrance differs sharply between variants, with V210I, V180I and M232R conveying lifetime risk in the range of 0.1 to 10 percent. Figures by variant are on penetrance and the variants hub.

What a pre-test session should cover

The informational part mirrors a diagnostic counselling session, with emphasis on the relevant variant’s phenotypic variation and its penetrance. Goldman and Vallabh then name the topics that are specific to predictive testing: in the United States, the Genetic Information Nondiscrimination Act; life and long-term care insurance; and reproductive options, noting that in vitro fertilisation with preimplantation genetic testing has been used successfully in genetic prion disease.

They also name options that are easy to omit and valuable to offer. Non-disclosure IVF with preimplantation genetic testing, where the embryo is selected without the parent learning their own status. Depositing DNA. And holding a test result in reserve for future use by the client or their family, meaning the sample is tested but the result is not opened.

Clients are strongly advised to bring a support person to both the counselling and the results session. The guidance suggests asking that person directly how they imagine the client would respond to a positive or negative result in the short and long term, whether they are worried about how they will cope, and whether the client would consider seeing a therapist.

Disclosure inside the family

This is where the difficult questions sit. There may be an ethical duty to warn, and not everyone will want to warn, often out of concern about raising anxiety in their children.

The approach Goldman and Vallabh recommend is to have the conversation before the result exists. The person being tested raises it hypothetically with relatives and asks whether they would want to know the result if the at-risk person chose to test. That preserves each relative’s right not to know and tells the client who to tell.

Parents hesitant to tell adult children should be forewarned that withholding can create situations nobody wanted, a pregnancy among them. Disclosing to adult children may cause anxiety and gives them the option of pursuing their own predictive testing. The right not to know covers this from the family’s side.

What the evidence says about the effect of testing

Useful to be able to state, because clients and their relatives often assume the worst. Many people report important benefits from receiving their genetic information regardless of the outcome. Relief from uncertainty can be a significant psychological factor, capable of more than compensating for an unwanted result, and the act of gathering information through testing can itself be an effective coping mechanism. A recent study in genetic prion disease echoed the broader finding that although having a genetic disease in the family is stressful, predictive testing does not increase that stress above baseline.

Goldman and Vallabh also note some indication that predictive testing rates in genetic prion disease are gradually rising, in keeping with increased genetic testing in neurology clinics generally and perhaps a greater openness among young adults.

None of this is a reason to encourage testing. Not testing remains a valid outcome of counselling, and the Israeli framework builds in delay rather than momentum: at least one month from counselling to blood sampling, and consideration of a six-month delay after acute bereavement or in acute emotional distress.

When the affected person cannot be tested in life

A common and solvable problem. Families overwhelmed by the affected person’s needs may be unable to pursue testing while that person is alive, and the guidance asks counsellors to lead a discussion on whether testing the affected person is in the best interests of that person and the family, then to offer the alternatives: banking DNA, and testing future autopsy tissue.

Two technical points belong in that conversation. Octapeptide repeat insertions are not typically detected by next-generation sequencing, so ordering providers must be mindful of the testing technique and its coverage. And the 2026 UK recommendations list obtaining tissue for PRNP testing, where blood was not taken in life, as one of the reasons for a post-mortem examination. Autopsy and brain donation covers how families experience that request.

Where results go

In the United States, the surveillance centre returns results to an ordering healthcare provider to be shared with the patient or family, and at the time Goldman and Vallabh wrote, predictive testing there was free of charge for those with a first-degree relative confirmed to have prion disease. The Israeli framework likewise has results returned to the referring team and disclosed in person by the clinician who gave the initial counselling. Either way, the named clinician is the pathway, so that name should be recorded and reachable.

Research and trials

Goldman and Vallabh frame clinical trials as foreseeable rather than available, and note that healthy at-risk individuals may be best positioned to benefit, which is part of their argument for expanding access to counselling and testing. The Israeli panel’s tenth recommendation is that research participation be offered. Participation is always an individual’s choice, and should be presented without any suggestion that testing is a route to treatment. Treatment research explained and how trials work cover what is and is not currently open.

What the systems still lack

The Israeli framework names its own gap plainly: no structured national post-test support programme exists, and support after a result comes mainly through health fund psychological services or research platforms. The 2026 UK recommendations describe anticipatory grief, stigma carried over from the BSE era, and mistrust following a long route to diagnosis as common in these families. A counsellor who can name those experiences aloud is often doing the most useful part of the work.