Familial Creutzfeldt-Jakob disease

A Finnish family is described with 9 cases of presenile dementia in 3 generations. The mean age at onset was 52 years (range 46--62 years). Progressive dementia, upper motor neuron signs, muscular rigidity, and twitching, irregular tremors were consistent features in the 6 clinically investigated patients and were associated with spongiform change in the cerebral cortex of one autopsy and two brain biopsy cases. The EEG showed progressive slowing without the occurrence of repetitive high-voltage complexes at any stage of the disease. The average duration of the disease (21 months, range 11--36 months) was longer than in the sporadic form of CJD. The occurrence of CJD within this family follows a pattern consistent with an autosomal dominant mode of inheritance, suggesting the possibility of vertical transmission of the presumptive causative agent for example by genomic integration or transplacental passage. However, the occurrence of the disease only through the paternal line of relationships and the presence of a discordant twin pair argue strongly against transplacental passage or transmission via mother's milk. Simple contact infection also seems unlikely, as conjugal cases were not found among the 7 married patients. The interval between the death of the last affected member in generation IV and the time of onset of the disease in the first affected member of generation V was 10 years. Thus setting a minimum incubation period if case-to-case transmission were occurring. To evaluate the role of a genetically determined susceptibility to infection studies on the HLA antigens and other genetic markers are in progress.