fatal familial insomnia


Summary: An autosomal dominant disorder characterized by degeneration of the THALAMUS and progressive insomnia. It is caused by a mutation in the prion protein (PRIONS).

Top Publications

  1. Gambetti P, Kong Q, Zou W, Parchi P, Chen S. Sporadic and familial CJD: classification and characterisation. Br Med Bull. 2003;66:213-39 pubmed
    ..The clinical and pathological features are summarised for each sporadic CJD subtype and familial CJD haplotype. ..
  2. Krasnianski A, Bartl M, Sanchez Juan P, Heinemann U, Meissner B, Varges D, et al. Fatal familial insomnia: Clinical features and early identification. Ann Neurol. 2008;63:658-61 pubmed publisher
    Our aim was to develop a detailed clinical description of fatal familial insomnia in a large patient group with respect to the M129V genotype. Data on 41 German fatal familial insomnia patients were analyzed...
  3. Piao Y, Kakita A, Watanabe H, Kitamoto T, Takahashi H. Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrPSc deposits in the brain. Neuropathology. 2005;25:144-9 pubmed
    ..Analysis of the prion protein gene (PRNP) showed no mutation, and homozygosity for methionine at codon 129. In conclusion, we considered that this patient had been suffering from sporadic, pathologically atypical fatal insomnia. ..
  4. Lugaresi E, Provini F. Fatal familial insomnia and agrypnia excitata. Rev Neurol Dis. 2007;4:145-52 pubmed
    This review summarizes the pioneering steps culminating in the identification of a novel disease, fatal familial insomnia (FFI), a hereditary prion disease...
  5. Jackson W, Borkowski A, Faas H, Steele A, King O, Watson N, et al. Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. Neuron. 2009;63:438-50 pubmed publisher
    ..We engineered knockin mice to express a PrP mutation associated with a distinct human prion disease, fatal familial insomnia (FFI). An additional substitution created a strong transmission barrier against pre-existing prions...
  6. Benito Leon J. Compassionate use of quinacrine in Creutzfeldt-Jakob disease fails to show significant effects. Neurology. 2005;64:1824; author reply 1824 pubmed
  7. Hagiwara K, Yamakawa Y, Hanada K. [Acquired human prion diseases--past and present issues]. Uirusu. 2009;59:155-65 pubmed
    ..To date, five instances of probable transfusion-mediated transmission of vCJD prion have been found in UK. Here we review the past and the present issues about the acquired human prion diseases. ..
  8. Llorens F, Zarranz J, Fischer A, Zerr I, Ferrer I. Fatal Familial Insomnia: Clinical Aspects and Molecular Alterations. Curr Neurol Neurosci Rep. 2017;17:30 pubmed publisher
    ..Although the development of a therapy is still a major challenge, recent findings represent a step toward understanding of the clinical and molecular aspects of FFI. ..
  9. Provini F, Cortelli P, Montagna P, Gambetti P, Lugaresi E. Fatal insomnia and agrypnia excitata: sleep and the limbic system. Rev Neurol (Paris). 2008;164:692-700 pubmed publisher
    b>Fatal familial insomnia, a human prion disease, Morvan's chorea, an autoimmune limbic encephalopathy, and delirium tremens, the well-known alcohol (or benzodiazepine [BDZ]) withdrawal syndrome, share a clinical phenotype largely ..

More Information


  1. Rodríguez Martínez A, Barreau C, Coupry I, Yague J, Sanchez Valle R, Galdós Alcelay L, et al. Ancestral origins of the prion protein gene D178N mutation in the Basque Country. Hum Genet. 2005;117:61-9 pubmed
    b>Fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD) are familial prion diseases with autosomal dominant inheritance of the D178N mutation. FFI has been reported in at least 27 pedigrees around the world...
  2. Iwahashi K, Aoki J. A review of smoking behavior and smokers evidence (chemical modification, inducing nicotine metabolism, and individual variations by genotype: dopaminergic function and personality traits). Drug Chem Toxicol. 2009;32:301-6 pubmed publisher
    ..Also, it is possible that persons with a low score in Openness may be refraining from smoking because they have a general negative impression toward smoking. ..
  3. Zhang J, Han J, Shi X, Guo W, Xia S, Shi Q, et al. [Studies on heredity rule of the first genealogy regarding fatal familial insomnia in Henan province]. Zhonghua Liu Xing Bing Xue Za Zhi. 2009;30:1-5 pubmed
    To investigate the epidemiological, genealogic characteristic, familial history of the families with fatal familial insomnia, its clinical and pathological features as well as the heredity rule of related genes...
  4. Billiard M. Fatal familial insomnia. Sleep Med Rev. 2005;9:337-8 pubmed
  5. Ayuso Blanco T, Urriza Mena J, Caballero Martínez C, Iriarte Franco J, Munoz R, Garcia Bragado F. [Fatal familiar insomnia: clinical, neurophysiological and histopathological study of two cases]. Neurologia. 2006;21:414-20 pubmed
    ..One of the most uncommon is the fatal familial insomnia (FFI), an entity characterized by sleep disorders and that is associated to a mutation in codon 178...
  6. Knight R, Brazier M, Collins S. Human prion diseases: cause, clinical and diagnostic aspects. Contrib Microbiol. 2004;11:72-97 pubmed
  7. Martinez Rodriguez J, Sanchez Valle R, Saiz A, Lin L, Iranzo A, Mignot E, et al. Normal hypocretin-1 levels in the cerebrospinal fluid of patients with fatal familial insomnia. Sleep. 2003;26:1068 pubmed
  8. Montagna P, Gambetti P, Cortelli P, Lugaresi E. Familial and sporadic fatal insomnia. Lancet Neurol. 2003;2:167-76 pubmed
    ..Intriguing clinicopathological correlations in FFI and SFI suggest a role for the thalamolimbic system in the regulation of sleep and other circadian functions. ..
  9. Rodríguez Martínez A, Alfonso Sanchez M, Peña J, Sanchez Valle R, Zerr I, Capellari S, et al. Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutation. Neurogenetics. 2008;9:109-18 pubmed publisher
    ..investigation of the genomic region surrounding the PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI) from several European countries, notably Spain...
  10. Elezgarai S, Fernandez Borges N, Eraña H, Sevillano A, Charco J, Harrathi C, et al. Generation of a new infectious recombinant prion: a model to understand Gerstmann-Sträussler-Scheinker syndrome. Sci Rep. 2017;7:9584 pubmed publisher
    ..that include Kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia. GSS is a genetically determined TSE caused by a range of mutations within the prion protein (PrP) gene...
  11. Wu L, Lu H, Wang X, Liu J, Huang C, Ye J, et al. Clinical Features and Sleep Analysis of Chinese Patients with Fatal Familial Insomnia. Sci Rep. 2017;7:3625 pubmed publisher
    ..sleep, abnormal sleep-wake transition and non-sleep disturbances as well as lab tests in Chinese fatal familial insomnia (FFI) subjects...
  12. Haïk S, Galanaud D, Linguraru M, Peoc h K, Privat N, Faucheux B, et al. In vivo detection of thalamic gliosis: a pathoradiologic demonstration in familial fatal insomnia. Arch Neurol. 2008;65:545-9 pubmed publisher
    ..From the neuroradiological point of view, fatal familial insomnia is probably the most challenging to diagnose because brain lesions are mostly confined to the thalamus...
  13. Soldevila M, Calafell F, Andres A, Yague J, Helgason A, Stefansson K, et al. Prion susceptibility and protective alleles exhibit marked geographic differences. Hum Mutat. 2003;22:104-5 pubmed
    ..all major continental groups, and six individuals affected by either Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI), were typed with a new single-reaction protocol method and were also sequenced, with total ..
  14. Kovács G. [Genetic background of human prion diseases]. Ideggyogy Sz. 2007;60:438-46 pubmed
    ..phenotype and comprise genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia. Base pair insertions may resemble Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker disease ..
  15. Culebras A. The neurology of insomnia series: preface to the third article. Rev Neurol Dis. 2007;4:143-4 pubmed
  16. Yu S, Zhang Y, Li S, Sy M, Sun S, Tien P, et al. Early onset fatal familial insomnia with rapid progression in a Chinese family line. J Neurol. 2007;254:1300-1 pubmed
  17. Zaborowski A. [Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Part II]. Psychiatr Pol. 2004;38:297-309 pubmed
    ..be a variant of familial CJD, kuru--probably a result of sporadic CJD's transmission by cannibalism, and fatal familial insomnia (FFI). Their clinical symptoms (and especially of the CJD), are nonspecific and sometimes variable...
  18. Thomas A, Klein J, Brockhaus Dumke A, Heiss W, Jacobs A, Petereit H. [Fatal familial insomnia: case presentation and discussion of typical clinical and imaging findings]. Nervenarzt. 2006;77:711-5 pubmed
    b>Fatal familial insomnia (FFI) is a hereditary prion disease caused by a mutation in codon 178 of the prion protein gene PRNP on chromosome 20...
  19. Sikorska B, Liberski P, Giraud P, Kopp N, Brown P. Autophagy is a part of ultrastructural synaptic pathology in Creutzfeldt-Jakob disease: a brain biopsy study. Int J Biochem Cell Biol. 2004;36:2563-73 pubmed
    ..TSEs)-Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) disease and fatal familial insomnia (FFI)...
  20. Chretien F, Le Pavec G, Vallat Decouvelaere A, Delisle M, Uro Coste E, Ironside J, et al. Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases. J Neuropathol Exp Neurol. 2004;63:1058-71 pubmed
    ..patients with Creutzfeldt-Jakob disease (8 sporadic, 2 familial, 2 iatrogenic, and 2 variant), and 4 with fatal familial insomnia (3 homozygous Met/Met at codon 129 of the PRNP gene, 1 heterozygous Met/Val), and 3 controls were ..
  21. Chiesa R, Restelli E, Comerio L, Del Gallo F, Imeri L. Transgenic mice recapitulate the phenotypic heterogeneity of genetic prion diseases without developing prion infectivity: Role of intracellular PrP retention in neurotoxicity. Prion. 2016;10:93-102 pubmed publisher
    ..diseases, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI). The reason for this variability is not known...
  22. Ayuso T, Tunon T, Erro M. [Sleep disorders in prion diseases]. An Sist Sanit Navar. 2007;30 Suppl 1:135-41 pubmed
    ..One of the most enigmatic and unusual is Fatal Familial Insomnia (FFI), a hereditary disorder characterised by loss of physiological sleep with oneiric stupor, autonomic ..
  23. Dimitri D, Jehel L, Durr A, Levy Soussan M, Andreux V, Laplanche J, et al. Fatal familial insomnia presenting as psychosis in an 18-year-old man. Neurology. 2006;67:363-4 pubmed
  24. Novakovic K, Villemagne V, Rowe C, Masters C. Rare genetically defined causes of dementia. Int Psychogeriatr. 2005;17 Suppl 1:S149-94 pubmed
    ..Awareness of these disorders, allied with recent advances in genetic, biochemical and neuroimaging techniques, may lead to early diagnosis, successful treatment and better prognosis. ..
  25. Montagna P. Fatal familial insomnia: a model disease in sleep physiopathology. Sleep Med Rev. 2005;9:339-53 pubmed
    b>Fatal Familial Insomnia (FFI) is characterized by loss of sleep, oneiric stupor with autonomic/motor hyperactivity and somato-motor abnormalities (pyramidal signs, myoclonus, dysarthria/dysphagia, ataxia)...
  26. Arata H, Takashima H. [Familial prion disease (GSS, familial CJD, FFI)]. Nihon Rinsho. 2007;65:1433-7 pubmed
    ..Normal cerebellar MRI and abnormal cerebral SPECT findings should be useful for early diagnosis of GSS (P102L). ..
  27. Franceschini A, Baiardi S, Hughson A, McKenzie N, Moda F, Rossi M, et al. High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions. Sci Rep. 2017;7:10655 pubmed publisher
    ..and MM2T, and a low sensitivity limited to variant CJD, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. While we found no difference in specificity between PQ-CSF and IQ-CSF, the latter showed a significant ..
  28. Chen J, Gao C, Shi Q, Shan B, Lei Y, Dong C, et al. Different expression patterns of CK2 subunits in the brains of experimental animals and patients with transmissible spongiform encephalopathies. Arch Virol. 2008;153:1013-20 pubmed publisher
    ..were observed in cerebella homogenates from one familial Creutzfeldt-Jakob disease (fCJD) case and one fatal familial insomnia (FFI) case...
  29. Taniguchi Y, Taketani T, Moriyama H, Moriki S, Nishimura K, Sato E, et al. Septic shock induced by Lecythophora mutabilis in a patient with mitochondrial encephalomyopathy. J Med Microbiol. 2009;58:1255-8 pubmed publisher
    ..On the basis of this we suggest that IFI caused by L. mutabilis should be suspected when a compromised host develops infection and eosinophilia, and that antifungal drugs that target beta-d-glucan are not advisable...
  30. Shi X, Han J, Zhang J, Shi Q, Chen J, Xia S, et al. Clinical, histopathological and genetic studies in a family with fatal familial insomnia. Infect Genet Evol. 2010;10:292-7 pubmed publisher
    We compared clinical data from two related Chinese patients with fatal familial insomnia (FFI) and collected information about their pedigree...
  31. Chen L, Shi Q, Zhang B, Zhang X, Wang J, Xiao K, et al. Proteomic Analyses for the Global S-Nitrosylated Proteins in the Brain Tissues of Different Human Prion Diseases. Mol Neurobiol. 2016;53:5079-96 pubmed publisher
    ..analysis of global S-nitrosylation in brain tissues of sporadic Creutzfeldt-Jakob disease (sCJD), fatal familial insomnia (FFI), and genetic CJD with a substitution of valine for glycine at codon 114 of the prion protein gene (..
  32. Sun C, Xia W, Liu Y, Jia G, Wang C, Yan C, et al. Agrypnia excitata and obstructive apnea in a patient with fatal familial insomnia from China: A case report. Medicine (Baltimore). 2017;96:e8951 pubmed publisher
    b>Fatal familial insomnia (FFI) linked to a D178N/129M haplotype mutation in the PRNP gene is the most common genetic prion disease in the Han Chinese population...
  33. Vanni S, Moda F, Zattoni M, Bistaffa E, De Cecco E, Rossi M, et al. Differential overexpression of SERPINA3 in human prion diseases. Sci Rep. 2017;7:15637 pubmed publisher
    ..n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), ..
  34. Majumder P, Chakrabarti O. Lysosomal Quality Control in Prion Diseases. Mol Neurobiol. 2018;55:2631-2644 pubmed publisher
    ..implicated in a number of neurodegenerative disorders such as scrapie, kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker and bovine spongiform encephalopathy...
  35. Allison W, Duval M, Nguyen Phuoc K, Leighton P. Reduced Abundance and Subverted Functions of Proteins in Prion-Like Diseases: Gained Functions Fascinate but Lost Functions Affect Aetiology. Int J Mol Sci. 2017;18: pubmed publisher
    ..prion diseases, wherein the normally folded prion protein, PrPC, is reduced in abundance in fatal familial insomnia patients and during the preclinical phase in animal models, apparently via proteostatic mechanisms...
  36. Benito Leon J. Combined quinacrine and chlorpromazine therapy in fatal familial insomnia. Clin Neuropharmacol. 2004;27:201-3 pubmed
    ..The objective of this paper was to report on 2 fatal familial insomnia patients whose overall condition worsened despite quinacrine and chlorpromazine treatment.
  37. Hazin R, Abuzetun J, Giglio P, Khan F. Agrypnia excitata: current concepts and future prospects in management. J Neuropsychiatry Clin Neurosci. 2009;21:126-31 pubmed publisher
    ..The following is an overview of agrypnia excitata with a particular emphasis placed upon each of the three individual conditions that constitute the syndrome with recommendations on appropriate management...
  38. Donadio V, Montagna P, Pennisi M, Rinaldi R, Di Stasi V, Avoni P, et al. Agrypnia Excitata: a microneurographic study of muscle sympathetic nerve activity. Clin Neurophysiol. 2009;120:1139-42 pubmed publisher
    ..AE is a common feature of acquired (i.e. Morvan's syndrome--MS) and genetic (i.e. fatal familial insomnia--FFI) conditions where a dysfunction of the thalamo-limbic system has been suggested...
  39. Konstantinov I, Carter M, Saxena P, Koniuszko M, Singh T, Alvarez J, et al. Prosthesis replacement in a calcified mitral annulus with reconstruction of the intervalvular fibrous body: the value of an alternative repair. Tex Heart Inst J. 2006;33:232-4 pubmed
    ..Placing sutures through healthy autologous tissues from outside the heart enabled secure replacement of the mitral prosthesis. This technique avoids extensive circumferential reconstruction of the mitral annulus. ..
  40. Ironside J, Ritchie D, Head M. Prion diseases. Handb Clin Neurol. 2017;145:393-403 pubmed publisher
    ..disease, variably protease-sensitive prionopathy, Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia, and kuru...
  41. Bandarra P, Pavarini S, Raymundo D, Corrêa A, Pedroso P, Driemeier D. Trema micrantha toxicity in horses in Brazil. Equine Vet J. 2010;42:456-9 pubmed publisher
    ..Trema micrantha poisoning should be evaluated as a possible cause in the diagnosis of equine hepatopathy and occasional secondary encephalopathy...
  42. Capellari S, Parchi P, Cortelli P, Avoni P, Casadei G, Bini C, et al. Sporadic fatal insomnia in a fatal familial insomnia pedigree. Neurology. 2008;70:884-5 pubmed publisher
  43. Smolensky M, Hermida R, Reinberg A, Sackett Lundeen L, Portaluppi F. Circadian disruption: New clinical perspective of disease pathology and basis for chronotherapeutic intervention. Chronobiol Int. 2016;33:1101-19 pubmed publisher
    ..kidney failure; depression; mania; bipolar disorder; Parkinson's disease; Smith-Magenis syndrome; fatal familial insomnia syndrome; autism spectrum disorder; asthma; byssinosis; cancers; hand, foot and mouth disease; post-..
  44. Takada L, Kim M, Metcalf S, Gala I, Geschwind M. Prion disease. Handb Clin Neurol. 2018;148:441-464 pubmed publisher
    ..into three forms: familial Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. This classification, however, occurred prior to the identification of PRNP, and although these forms are ..
  45. Synofzik M, Bauer P, Schols L. Prion mutation D178N with highly variable disease onset and phenotype. J Neurol Neurosurg Psychiatry. 2009;80:345-6 pubmed publisher
    ..and pathological overlap for patients with the D178N mutation, suggesting a continuous spectrum between fatal familial insomnia and Creutzfeldt-Jakob Disease phenotype...
  46. Friedrich M, Korte R, Portero C, Arzberger T, Kretzschmar H, Zerr I, et al. [Fatal familial insomnia--a rare differential diagnosis in dementia]. Fortschr Neurol Psychiatr. 2008;76:36-40 pubmed publisher
    b>Fatal familial insomnia (FFI)--first reported in 1986--is a hereditary prion disease with autosomal-dominant inheritance, caused by a missense-mutation at codon 178 of the prion-protein gene (PRNP) on chromosome 20...
  47. Kawashima T. [Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia and less common human prion diseases]. Nihon Rinsho. 2003;61 Suppl 3:17-21 pubmed
  48. Calandra Buonaura G, Provini F, Guaraldi P, Plazzi G, Cortelli P. Cardiovascular autonomic dysfunctions and sleep disorders. Sleep Med Rev. 2016;26:43-56 pubmed publisher
    ..from a common pathogenetic mechanism affecting both autonomic cardiovascular control and sleep, as in fatal familial insomnia, or it may be mainly caused by the sleep disorder, as observed in obstructive sleep apnoea...
  49. Wermke M, Teipel S, Fuchsberger T, Kretzschmar H, Westner I, Schröder M, et al. Frontal diaschisis in a German case of fatal familial insomnia. J Neurol. 2006;253:1510-2 pubmed
  50. Gao C, Shi Q, Wei J, Zhou W, Xiao K, Wang J, et al. The associations of two SNPs in miRNA-146a and one SNP in ZBTB38-RASA2 with the disease susceptibility and the clinical features of the Chinese patients of sCJD and FFI. Prion. 2017;: pubmed publisher
    ..and rs57095329) and one locus in ZBTB38-RASA2 (rs295301) of 561 Chinese patients of sCJD and 31 cases of fatal familial insomnia (FFI) were screened by PCR and sequencing...
  51. Gauczynski S, Krasemann S, Bodemer W, Weiss S. Recombinant human prion protein mutants huPrP D178N/M129 (FFI) and huPrP+9OR (fCJD) reveal proteinase K resistance. J Cell Sci. 2002;115:4025-36 pubmed
    ..of recombinant mutant prion proteins that are associated with inherited human prion diseases such as fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD)...
  52. Gaudino S, Gangemi E, Colantonio R, Botto A, Ruberto E, Calandrelli R, et al. Neuroradiology of human prion diseases, diagnosis and differential diagnosis. Radiol Med. 2017;122:369-385 pubmed publisher
    ..g. Gerstmann-Straussler-Scheinker disease, fatal familial insomnia, and inherited CJD), and acquired or infectious (e.g. Kuru, iatrogenic CJD, and variant CJD)...
  53. Sasaki K, Doh ura K, Wakisaka Y, Tomoda H, Iwaki T. Fatal familial insomnia with an unusual prion protein deposition pattern: an autopsy report with an experimental transmission study. Neuropathol Appl Neurobiol. 2005;31:80-7 pubmed
    ..a post-mortem examination on a Japanese patient who had a prion protein gene mutation responsible for fatal familial insomnia (FFI)...