Hereditary Creutzfeldt-Jakob disease and fatal familial insomnia

Hereditary Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI) are familial prion diseases. They are associated with the autosomal-dominant inheritance of mutations in the prion protein gene (PRNP), and have a diverse disease phenotype that is determined by a combined effect of the PRNP mutation, codon 129 polymorphism, and the presence of a distinct conformer of pathogenic prion protein (PrP). Understanding of the relationship between genotype and disease phenotype in familial prion disease will provide important insights into the pathogenesis of prion disease. This article summarizes the studies on hereditary CJD and FFI in terms of their genetics, epidemiology, clinical and pathologic features, and characteristics of pathogenic PrP.