The Gerstmann-Sträussler-Scheinker syndrome, is a disease transmitted by autosomal dominant inheritance characterized by nonsense mutations of the prion protein associated with specific neuropathological lesions-multicentric amyloid plaques labelled by antibodies directed against the prion protein. This restrictive definition justifies retaining the name of Gerstmann-Sträussler-Scheinder syndrome and excludes observations of hereditary prion diseases without multicentric amyloid plaques and sporadic forms with multicentric plaques. The main feature of these different observations is their polymorphous clinical presentation which varies not only between families with the same mutation but also with a given family. The underlying mechanisms of the phenotypic polymorphism remain uncertain.