Creutzfeldt-Jacob disease (CJD) is a rare, neurodegenerative, spongiform encephalopathy caused by a subacute infection with a pathogenic sterically altered prion protein (PrP). The disease-causing conformational change in the PrP may be infection-related or due to pathogenic variants in the coding gene PRNP. The disease has an onset between the 3rd and 8th decade of life, and the average age of onset is 61.5 years. Most patients die within one year of disease onset.
CJD occurs worldwide with an incidence of approximately 1:1,000,000. The familial form of CJD is comparatively common in Chileans and Libyan Jews (frequency 1:20,000); the proportion of familial CJD cases is about 40-50% in Jews of Libyan origin. Approximately 10% of all cases follow an autosomal dominant mode of inheritance.
A pathogenic variant in the PRNP gene (E200K) that is considered to be causative has been identified in more than 70% of the familial CJD cases investigated worldwide. In addition, some genetic variants in the regulatory regions of the PRNP gene have recently been detected that appear to be associated with the sporadic form of CJD (sCJD). Furthermore, a variant form of CJD (vCJD) has been described in connection with bovine spongiform encephalopathy in cattle which appears to be transmissible and thus acquired.
Zerr et al. 2018, Creutzfeldt-Jakob-Krankheit, S1-Leitlinie in: D Ges Neurol (Hrsg.) www.dgn.org/leitlinien / Minikel et al. 2016, Sci Transl Med 8:322 / Schelzke et al. 2013, Dement Geriat Coqn Disard 35:229 / Gozke et al. 2008, Cases J 1:146 / Michalczyk et al. 2007, Histol Histopathol 22:1149 / Hilton et al. 2006, J Pathol 208:134 / Johnson et al. 2005, Lancet Neurol 4:635 / McCormack et al. 2002, Gene 288:139 / Colombo et al. 2000, Am J Hum Genet, 67:528 / Lee et al. 1999, Am J Hum Mut 64:1063 / Prusiner et al. 1991, Science 252:1515