Walsh & Hoyt: Genetic Human Prion Disease

Approximately 1015% of human prion diseases are genetic or inherited, and associated with an identifiable defect in the PRNP gene, for an overall incidence of 1 in 10 million. This figure may grow with increasing genetic knowledge and the greater recognition of disease in individuals with a negative family history. In one survey of 57 patients with CJD, six of the nine patients with PrP gene mutations reported a negative family history. Penetrance of the autosomal-dominant prion diseases appears to be complete and age-dependent. The three main phenotypes that comprise the human familial prion diseases are familial CJD (fCJD), Gerstmann-Straussler-Scheinker (GSS) disease, and fatal familial insomnia (FFI).