Highly-penetrant disease-causing PRNP mutations cause diseases historically classified into Gerstmann-Straussler-Scheinker (GSS) syndrome, fatal familial insomnia (FFI) and familial CJD (fCJD)6, although this fails to encapsulate the diversity of phenotypes resulting from octapeptide repeat insertions (OPRIs) and the more recently described peripheral systemic amyloidosis secondary to the PRNP Y163X mutation7,8. This evidence concerns the gene PRNP and fatal familial insomnia.