Family planning options

What routes are described?

A 2022 review of the genetics of human prion diseases lists two main routes for carriers who want biological children without the variant: preimplantation genetic diagnosis with IVF, and in utero testing. It also states that preimplantation testing can be done without the prospective parent learning their own status.

The 2026 Israeli practice framework sets out the same ground in more operational terms and distinguishes two forms of preimplantation genetic testing. Direct PGT tests embryos for the known family variant. Exclusion PGT selects embryos that did not inherit the at-risk allele from the affected grandparent, while the parent’s own genetic status remains unknown. In Israel, exclusion PGT is described as available at tertiary centres for first- and second-degree relatives.

For prenatal diagnosis the framework gives the two standard procedures and their timing: chorionic villus sampling at about 11 to 12 weeks, and amniocentesis at about 17 to 23 weeks. The panel noted that decisions about termination raise ethical questions beyond the scope of their paper, and this page takes the same position.

Why does exclusion testing exist?

Because a person can want to avoid passing on a variant without wanting to know whether they carry it. The two questions are separable, and exclusion testing separates them.

The trade-off is that exclusion testing discards embryos that carry the grandparental allele regardless of whether the variant is on it, so where the parent is in fact not a carrier, embryos that were never at risk are not transferred. Couples are counselled about that before starting, and it is the main reason some choose direct testing instead.

A related approach appears in the prion disease literature as non-disclosure PGD, in which the clinical team knows the parent’s genotype and the parent does not. The right not to know covers the wider question of declining predictive testing.

What is the published prion disease experience?

Small, and worth describing exactly. The reference case is a 2014 JAMA Neurology report. A 27-year-old asymptomatic woman from a Gerstmann-Straussler-Scheinker family, found on predictive testing to carry PRNP F198S, underwent IVF with preimplantation genetic diagnosis. Of 12 fertilised oocytes, polar body and blastomere analysis identified six without the variant. Two were transferred and three remaining viable embryos were frozen. A twin pregnancy followed, with slightly premature but healthy infants who had met developmental milestones at 27 months.

The authors described it, to their knowledge, as the first published report of IVF with PGD for a genetic prion disease. They noted that non-disclosure PGD was discussed as an option with this couple; the patient chose to learn her status.

That is one family, one variant and one follow-up period. It establishes that the route is technically available in prion disease, and it does not provide success rates. General IVF and preimplantation testing success rates come from the fertility service, not from the prion literature, and they depend on age and clinic.

How is approval handled?

Through national systems that differ considerably.

In the UK, preimplantation genetic testing for monogenic conditions is carried out by licensed centres, and the HFEA maintains a list of conditions authorised for testing. Applications to add a condition come from licensed UK centres, and the HFEA aims to follow OMIM naming, so searching by OMIM number is more reliable than by condition name. The HFEA states explicitly that a condition’s absence from the list does not necessarily mean it has been refused, and directs enquiries to its PGT-M team. The practical answer for a specific condition therefore comes from the treating centre or the HFEA rather than from a published list.

In Israel, the framework recommends that preimplantation and prenatal testing decisions be made case by case with individualised decision-making, and that counselling and testing be publicly funded to ensure equitable access.

Elsewhere, availability, funding and the legal position all vary. The only reliable source for a particular family is a clinical genetics service in their own country.

What has to happen first?

Genetic counselling, before any of this. The Israeli framework sets out a four-step sequence for predictive testing in relatives: counselling, psychological assessment, blood sampling, and disclosure in person by the same clinician who gave the counselling, with at least a month between counselling and sampling, expedited in special circumstances such as pregnancy. Testing is not offered under 18, and people in acute distress, such as shortly after a relative’s diagnosis or death, are encouraged to wait at least six months.

Those timings interact with reproductive planning, which is why the framework allows expedition during a pregnancy and why this is a conversation to open early rather than at the point of decision. Genetic counselling comes first sets out the process, and inherited prion disease explained the underlying genetics.

Is the 50 percent figure reliable?

It is the figure in current guidance, and one recent study questions it. A 2025 European Journal of Neurology analysis of 24 pedigrees, 65 nuclear families and 151 offspring reported transmission of 67.1 percent for D178N, with a 95 percent confidence interval of 56.3 to 77.9, and 70.5 percent for E200K, interval 60.4 to 80.6, with a combined figure of 68.9 percent. The authors proposed meiotic drive, gametic competition or embryonic selection as possible mechanisms.

The study is retrospective, 18 percent of genotypes were inferred rather than tested, the D178N families are concentrated in the Basque population, and the authors called for prospective validation across populations before counselling protocols change. Families who find the paper should be told both the result and the caveat, and the figure used in their own counselling is the one their genetics service applies.

Where next?

Genetics and family risk is the hub for this section, and genetic counselling comes first the next step for anyone considering any of this.

This page describes published practice and literature. It is not medical, genetic or legal advice, it does not recommend any option over another, and nothing here says what is available or appropriate for a particular person. Those questions belong with a clinical genetics service and a fertility service.