Data for this review were obtained from our personal files and searches of Medline, Current Contents, and references from relevant articles. Search terms were “fatal familial insomnia”, “prion” and “Creutzfeldt-Jakob disease (CJD)”. All abstracts and full papers related to the topic were assessed. We included data from 1986, when FFI was first described, to the present. Papers published in English and French were reviewed.
ReviewFamilial and sporadic fatal insomnia
Section snippets
Clinical features of FFI
FFI affects both sexes equally in an autosomal dominant manner with (probable) high penetrance. Onset is between 36 years and 62 years of age (mean 51 years [SD 7·1]). FFI is uniformly fatal. The disease duration, defined from the onset of insomnia, varies from 8 months to 72 months (mean 18·4 months [SD 17·3]). Patients in the original pedigrees died after either a short (8–11 months; mean 9·1 months [SD 1·1]) or a long (11–72 months; mean 30·8 months [SD 21·3]) disease course.14 Most patients
Pathophysiology of FFI
FFI has led to interesting speculations and opened new avenues in clinical science because, as a disease, it lies at the intersection of two areas of scientific research: the complex and still unclear pathophysiology of the prion diseases and the mechanisms of regulation of sleep and circadian rhythms. These special characteristics have made FFI an intriguing and even controversial issue.
Unsolved issues in FFI
The study of FFI has yielded important insights into several areas of neurological investigation including the relevance of the thalamus and related limbic cortical areas in the control of autonomic and circadian rhythms and the concept of agrypnia excitata. This research has further widened the clinical and pathological range of prion diseases and introduced a novel molecular mechanism of disease inheritance and phenotypic variability of a genetic disease with the first identification of human
Search strategy and selection criteria
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Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity
Science
Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family
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Experimental transmission of a kuru-like syndrome to chimpanzees
Nature
Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome
Nature
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