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Familial creutzfeldt-jakob disease in France: Epidemiological implications

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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-Straiissler 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 pathogenesic mechanism in several neurological diseases, including Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT).

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References

  1. Asher D.M., Masters C.L., Gajdusek D.C. and Gibbs C.J. Jr. (1983): Familial spongiform encephalopathies. In: S.S. Kety, L.P. Rowland, R.L. Sidman and S.W. Matthysse (EDs.), Genetics of Neurological and Psychiatric Disorders, Raven Press, New York, pp. 273–291.

    Google Scholar 

  2. Baker H.F., Ridley R.M. and Crow T.J. (1985): Experimental transmission of an autosomal dominant spongiform encephalopathy: does the infectious agent originate in the human genome? -Brit. Med. J., 291: 299–302.

    Article  CAS  Google Scholar 

  3. Bianco C. (1984): Un cas de démence familiale — syndrome de Gerstmann-Straüssler (Actes du Club Français de Neuropathologie, Séance du samedi 23 juin, 1984). -Rev. Neurol. (Paris), 140: 601.

    Google Scholar 

  4. Bockman J.M., Kingsbury D.T., McKinley M.P., Bendheim P.E. and Prusiner S.B. (1985): Creutzfeldt-Jakob disease prion proteins in human brains. -N.Engl. J. Med., 312: 74–78.

    Article  Google Scholar 

  5. Bonduelle M., Escourolle R., Bouygues P., Lormeau G., Ribadeau Dumas J.L. and Merland J.J. (1971): Maladie de Creutzfeldt-Jakob familiale — observation anatomo-clinique. -Rev. Neurol. (Paris), 125: 197–209.

    CAS  Google Scholar 

  6. Breitner J.C.S. and Folstein M.F. (1984): Familial nature of Alzheimer's disease. -N. Engl. J. Med., 311: 192.

    CAS  PubMed  Google Scholar 

  7. Brown P., Cathala F., Sadowsky D. and Gajdusek D.C. (1979): Creutzfeldt-.Iakob disease in France: II. Clinical characteristics of 124 consecutive verified cases during the decade 1968–1977. -Ann. Neurol., 6: 430–437.

    Article  CAS  Google Scholar 

  8. Brown P., Cathala F., Raubertas R., Castaigne P. and Gajdusek D.C. ( ): Creutzfeld-Jakob disease in France: Conclusions from a 15-year epidemiologic study (manuscript in preparation).

  9. Buge A., Escourolle R., Brion S., Rancurel G., Hayw J.J., Mehaut M., Gray F. and Gajdusek D.C. (1978): Maladie de Creutzfeldt-Jakob familiale — étude clinique et anatomique de trois cas sur huit répartis sur trois générations. Transmission au singe écureuil. -Rev. Neurol. (Paris). 134: 165–181.

    CAS  Google Scholar 

  10. Cathala F., Chatelain J., Brown P., Dumas M. and Gajdusek D.C. (1980): Familial Creutzfeldt-Jakob disease — autosomal dominance in 14 members over 3 generations. -J. Neurol. Sci., 47: 343–351.

    Article  CAS  Google Scholar 

  11. Cathala F., Brown P., Lecanuet P. and Gajdusek D.C. (1985): High incidence of Creutzfeldt-Jakob disease in North African immigrants to France. -Neurology, 35: 894–895.

    Article  CAS  Google Scholar 

  12. Chesebro B., Race R., Wehrly K., Nishio J., Bloom M., Lechner D., Bergstrom S., Robbins K., Mayer L., Keith J., Garon C. and Haase A. (1985): Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. -Nature, 315: 331–333.

    Article  CAS  Google Scholar 

  13. Dickinson A.G. and Meikle V.M.H. (1969): A comparison of some biological characteristics of the mouse-passaged scrapie agents, 22A and ME7. -Gen. Res. (Camb.), 13: 213.

    Article  CAS  Google Scholar 

  14. Dickinson A.G. and Meikle V.M.H. (1971): Hostgenotype and agent effects in scrapie incubation: chance in allelic interaction with different strains of agent. -Mol. Gen. Genet., 112: 73.

    Article  CAS  Google Scholar 

  15. Ferber R.A., Wiesenfeld S.L., Roos R.P., Bobowick A.R., Gibbs C.J. Jr. and Gajdusek D.C. (1973): Familial Creutzfeldt-Jakob disease — transmission of the familial disease to primates. In: A. Subirana, J.M. Espadaler and E.H. Burrows (Eds.), Neurology. Proceedings of the Tenth International Congress of Neurology, Genetic and Transmissible Dementias, Chapter 3, Barcelona, September 8–15, 1973, Excerpta Medica, International Congress Series No. 319, pp. 358–380.

  16. Foncin J.F., Salmon D., Supino-Viterbo V., Feldman R.G., Macchi G., Mariotti P., Scoppetta C., Caruso G. and Bruni A.C. (1985): Démence présénile d'Alzheimer transmise dans une famille étendue. -Rev. Neurol. (Paris), 141: 194–202.

    CAS  Google Scholar 

  17. Gajdusek D.C. (1985): Hypothesis: interference with axonal transport of neurofilament as a common pathogenetic mechanism in certain diseases of the central nervous system. -N. Engl. J. Med., 312: 714–719.

    Article  CAS  Google Scholar 

  18. Galvez S., Cartier L., Monari M. and Araya G. (1983): Familial Creutzfeldt-Jakob disease in Chile. -J. Neurol. Sci., 59 : 139–147.

    Article  CAS  Google Scholar 

  19. Guiot G. and Brion S. (1953): Traitement des mouvements anormaux par la coagulation pallidale — technique et résultats. -Rev. Neurol. (Paris), 89: 578–580.

    CAS  Google Scholar 

  20. Kahana E., Alter M., Braharn J. and Sofer D. (1974): Creutzfeldt-Jakob disease: Focus among Libyan Jews in Israel. -Science 183: 90–91.

    Article  CAS  Google Scholar 

  21. Kingsbury D.T., Kasper K.C., Stites D.P., Watson J.D., Hogan R.N. and Prusiner S.B. (1983): Genetic control of scrapie and Creutzfeldt-Jakob disease in mice. -J. Immunol., 131 : 491–496.

    CAS  PubMed  Google Scholar 

  22. Marchand L. and Abély X. (1948)-Atrophie et sclérose cérébrale rapidement évolutive chez une femme de 40 ans (maladie de Creutzfeldt-Jakob). -Ann. Med.-Psychol., 106: 32.

    Google Scholar 

  23. Masters C.L. ( ): The epidemiology of Creutzfeldt-Jakob disease: studies on the natural mechanisms of transmission. In: S.B. Prusiner and M.P. McKinley (Eds.), Prions Causing Scrapie and Creutzfeldt-Jakob Disease, Academic Press, Orlando, (In Press).

  24. Masters C.L., Gajdusek D.C. and Gibbs C.J. Jr. (1981a): Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Straüssler syndrome — with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies. -Brain, 104: 559–588.

    Article  CAS  Google Scholar 

  25. Masters C.L., Gajdusek D.C. and Gibbs C.J. Jr. (1981b): The familial occurrence of CreutzfeldtJakob disease and Alzheimer's disease. -Brain, 104: 535–558.

    Article  CAS  Google Scholar 

  26. Multhaup G., Diringer H., Hilmert H., Prinz H., Heukeshoven J. and Beyreuther K. (1985): The protein component of scrapie-associated fibrils is a non-infectious glycosylated low molecular weight protein — scrapie-associated fibril protein. -Embo J., 4: 1495–1501.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Neugut R.H., Neugut A.I., Kahana E., Stein Z. and Alter M. (1979): Creutzfeldt-Jakob disease: Familial clustering among Libyan-born Israelis. -Neurology, 29: 225–251.

    Article  CAS  Google Scholar 

  28. Oesch B., Westaway D., Wälchli M., McKinley M.P., Kent S.B.H., Aebersold R., Barry R.A., Tempst P., Teplow D.B., Hood L.E., Prusiner S.B. and Weiss mann C. (1985): A cellular gene encodes scrapie PrP 27-30 protein. -Cell, 40: 735–746.

    Article  CAS  Google Scholar 

  29. Vallat J.M., Dumas M., Corvisier N., Leboutet M.J., Loubet A., Dumas P. and Calhala F. (1983): Familial Creutzfeldt-Jakob disease with extensive degeneration of white spatter — ultrastructure of peripheral nerve. -J. Neurol. Sci., 61: 261–275.

    Article  CAS  Google Scholar 

  30. Will R.G. and Matthews W.B. (1984): A retrospective study of Creutzfeldt-Jakob disease in England and Wales 1970–79 1: clinical features. -J. Neurol. Neurosurg. Psych., 47: 134–140.

    Article  CAS  Google Scholar 

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Author notes

  1. H. Brown

    Present address: Searle Research and Development Sophia Antipolis, B.P. 23 06561, Valbonne Cedex, France

Authors and Affiliations

  1. Laboratoire de Neurovirologie, Hôpital de la Salpétrière, 47, Bd. de l'Hôpital, 75651, Paris, France

    H. Brown, F. Cathala & J. Chatelain

  2. Laboratory of Central Nervous System Studies, NINCDS, National Institutes of Health, 20892, Bethesda, Maryland, USA

    P. Brown & D. C. Gajdusek

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  1. H. Brown
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  2. F. Cathala
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  4. J. Chatelain
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  5. D. C. Gajdusek
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Brown, H., Cathala, F., Brown, P. et al. Familial creutzfeldt-jakob disease in France: Epidemiological implications. Eur J Epidemiol 2, 252–264 (1986). https://doi.org/10.1007/BF00419489

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