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Familial Creutzfeldt-Jakob disease in France: epidemiological implications
Insights
Familial Creutzfeldt-Jakob disease (CJD) cases were identified, with Mediterranean Jewish populations showing higher prevalence. Early-life horizontal transmission and genetic susceptibility may play roles in CJD pathogenesis.
Area of Science:
- Neurology
- Genetics
- Epidemiology
Background:
- Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder.
- Familial cases represent a subset of CJD, suggesting a genetic component.
Purpose of the Study:
- To investigate the characteristics and transmission patterns of familial Creutzfeldt-Jakob disease (CJD).
- To explore potential genetic factors and transmission mechanisms within affected families.
Main Methods:
- Retrospective analysis of CJD cases in continental France (1968-1982).
- Genealogical investigation to identify familial cases and affected relatives.
- Clinical and epidemiological data analysis, including age at death and disease duration.
Main Results:
- 38 familial CJD cases identified, with 6 affected families.
- Mediterranean Jewish populations, particularly Tunisian Jews, showed a disproportionately high incidence.
- Familial CJD cases exhibited earlier age at death and longer disease duration compared to sporadic CJD.
- Evidence suggested potential horizontal transmission early in life and possible genetic susceptibility linked to amyloid-type proteins.
Conclusions:
- Familial CJD has distinct epidemiological and clinical features, including ethnic predispositions.
- Genetic factors and potential early-life environmental exposures likely contribute to CJD pathogenesis.
- A nosological link between CJD and Gerstmann-Straüssler syndrome (GSS) is suggested.
- The findings contribute to understanding the complex etiology of prion diseases and their relationship to other neurodegenerative disorders like Alzheimer's disease.
Abstract:
Of 329 patients dying of Creutzfeldt-Jakob disease (CJD) in continental France between 1968 and 1982, 19 (6%) were familial cases. Genealogical investigation permitted the identification of 19 additional cases, bringing the total number of familial CJD cases reported here to 38. There are 6 definitely affected families, yielding an average of 6.3 cases per family. Mediterranean Jews account for one-third of all the cases, with Tunisian Jews constituting two-thirds of this ethnic group. Males and females are equally affected. The overall rate of occurrence (47.3%) is consistent with autosomal dominant transmission, but wide variations in individual pedigrees (26.7%-80%) leave this hypothesis open to scrutiny. Age at death is 10 to 15 years lower in familial than in sporadic CJD, suggesting the possible inheritance of "short incubation" genes in certain CJD families. Disease duration is longer in familial than in sporadic CJD, but this could be the effect of ascertainment bias. There is no evidence for maternal lineage. While members of a given family tend to die within the same age bracket, our data fail to discriminate between vertical transmission and common source exposure as hypothetical transmission mechanisms within affected families. CJD occurrence in a woman related by marriage to an unaffected branch of a CJD family, but who was raised in early childhood by the affected branch, argues in favor of horizontal transmission early in life. Analysis of death intervals and geographic/temporal separations suggests minimal incubation periods of up to 43 years. A family combining clinico-pathological features of CJD and the Gerstmann-Straüssler syndrome (GSS) indicates a nosological relationship between the two. The "genetic susceptibility" of members of CJD-affected families may be due to accelerated derepression of normally repressed host genes, coding for abnormal amyloid-type proteins. Accumulation of these proteins may play an important role in the pathogenesis of CJD and scrapie, and constitute a common pathogenetic mechanism in several neurological diseases, including Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT).