THE ORIGINAL GERSTMANN-STRAUSSLER-SCHEINKER FAMILY OF AUSTRIA - DIVERGENT CLINICOPATHOLOGICAL PHENOTYPES BUT CONSTANT PRP GENOTYPE

We present new data on the original Austrian kindred with Gerstmann-St raussler-Scheinker disease (GSS) which encompasses currently 221 membe rs in 9 generations. The mode of inheritance is autosomal dominant. Pr edominant clinical features are slowly progressive ataxia and late imp airment of higher cerebral functions. In contrast, a recent case with proven P102L mutation of the PRNP gene had rapidly developing dementia and severe cortical damage indistinguishable from the clinicopatholog ical phenotype of Creutzfeldt-Jakob disease (CJD). PRNP codon 129 was homozygous for methionine in both the historic and recent cases. Neuro pathology confirms spongiosis of variable degree and numerous protease resistant / prion protein (PrP) amyloid plaques scattered throughout most of the brain as constant features in this family. Some amyloid de posits are surrounded by dystrophic neurites with accumulation of phos phorylated neurofilaments and abnormal organelles, reminiscent of Alzh eimer-type plaques. Severe telencephalic damage and a synaptic-type fi ne granular immunoreactivity in laminar distribution in the cortex wit h anti-PrP after hydrated autoclaving of sections were seen only in th e recent patient. In conclusion, factors in addition to the PRNP genot ype at codons 102 and 129 must play a role in determining clinicopatho logical characteristics of this inherited brain amyloidosis.