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Fatal familial insomnia(FFI)

MedGen UID:
104768
Concept ID:
C0206042
Disease or Syndrome
Synonyms: FFI
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: FFI - Familial fatal insomnia (83157008); Familial fatal insomnia (83157008); Fatal familial insomnia (83157008)
 
Gene (location): PRNP (20p13)
OMIM®: 600072
Orphanet: ORPHA466

Disease characteristics

Excerpted from the GeneReview: Genetic Prion Diseases
Genetic prion diseases generally manifest with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. Familial Creutzfeldt-Jakob disease (fCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI) represent the core phenotypes of genetic prion disease. Note: A fourth clinical phenotype, known as Huntington disease like-1 (HDL-1) has been proposed, but this is based on a single report, and the underlying pathologic features would categorize it as GSS. Although it is clear that these four subtypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset ranges from the third to ninth decade of life. The course ranges from a few months to several years (typically 5-7 years; in rare instances, >10 years). [from GeneReviews]
Authors:
James A Mastrianni   view full author information

Additional descriptions

From OMIM
Fatal familial insomnia is a prion disorder showing autosomal dominant inheritance. It is clinically characterized by insomnia with or without a diurnal dreaming state, hallucinations, delirium, and dysautonomia preceding motor and cognitive deterioration. FFI is specifically associated with the asp178-to-asn mutation of the PRNP gene (D178N; 176640.0010) when the amino acid at position 129 is methionine (M129V; 176640.0005). The D178N mutation and the val129 allele results in Creutzfeldt-Jacob disease (CJD; 123400) (see 176640.0007) (Goldfarb et al., 1992). CJD typically presents with dementia, ataxia, myoclonus, and other abnormal movements; however, there is considerable clinical and pathologic overlap between FFI and CJD, and some individuals with D178N and met129 may present with a phenotype suggestive of CJD. Thus, FFI and CJD may be viewed as extremes of a phenotypic spectrum (summary by Zarranz et al., 2005).  http://www.omim.org/entry/600072
From GHR
Prion disease represents a group of conditions that affect the nervous system in humans and animals. In people, these conditions impair brain function, causing changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements, particularly difficulty with coordinating movements (ataxia). The signs and symptoms of prion disease typically begin in adulthood and worsen with time, leading to death within a few months to several years.  https://ghr.nlm.nih.gov/condition/prion-disease

Clinical features

Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Decrease in existing BODY WEIGHT.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Constipation means that a person has three or fewer bowel movements in a week. The stool can be hard and dry. Sometimes it is painful to pass. At one time or another, almost everyone gets constipated. In most cases, it lasts a short time and is not serious. . There are many things you can do to prevent constipation. They include - Eating more fruits, vegetables and grains, which are high in fiber. - Drinking plenty of water and other liquids. - Getting enough exercise. - Taking time to have a bowel movement when you need to. - Using laxatives only if your doctor says you should. - Asking your doctor if medicines you take may cause constipation. . It's not important that you have a bowel movement every day. If your bowel habits change, however, check with your doctor. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Pathologic Function
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Finding
A fever is a body temperature that is higher than normal. It is not an illness. It is part of your body's defense against infection. Most bacteria and viruses that cause infections do well at the body's normal temperature (98.6 F). A slight fever can make it harder for them to survive. Fever also activates your body's immune system. Infections cause most fevers. There can be many other causes, including. - Medicines. - Heat exhaustion. - Cancers. - Autoimmune diseases. Treatment depends on the cause of your fever. Your health care provider may recommend using over-the-counter medicines such as acetaminophen or ibuprofen to lower a very high fever. Adults can also take aspirin, but children with fevers should not take aspirin. It is also important to drink enough liquids to prevent dehydration.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Fatal familial insomnia in Orphanet.

Recent clinical studies

Etiology

Forloni G, Tettamanti M, Lucca U, Albanese Y, Quaglio E, Chiesa R, Erbetta A, Villani F, Redaelli V, Tagliavini F, Artuso V, Roiter I
Prion 2015;9(2):75-9. doi: 10.1080/19336896.2015.1027857. PMID: 25996399Free PMC Article
Tian C, Liu D, Xiang W, Kretzschmar HA, Sun QL, Gao C, Xu Y, Wang H, Fan XY, Meng G, Li W, Dong XP
Mol Neurobiol 2014 Oct;50(2):473-81. Epub 2014 Jun 7 doi: 10.1007/s12035-014-8758-x. PMID: 24902808
Gemignani A, Laurino M, Provini F, Piarulli A, Barletta G, d'Ascanio P, Bedini R, Lodi R, Manners DN, Allegrini P, Menicucci D, Cortelli P
Sleep Med 2012 Aug;13(7):946-52. Epub 2012 May 19 doi: 10.1016/j.sleep.2012.03.007. PMID: 22609023
Capellari S, Strammiello R, Saverioni D, Kretzschmar H, Parchi P
Acta Neuropathol 2011 Jan;121(1):21-37. Epub 2010 Oct 27 doi: 10.1007/s00401-010-0760-4. PMID: 20978903
Saitoh Y, Ogawa M, Naito Y, Komatsuzaki Y, Tagaya H, Arima K, Tamaoka A, Kitamoto T, Murata M
Neurology 2010 Jan 5;74(1):86-9. doi: 10.1212/WNL.0b013e3181c7da09. PMID: 20038778

Diagnosis

Krasnianski A, Sanchez Juan P, Ponto C, Bartl M, Heinemann U, Varges D, Schulz-Schaeffer WJ, Kretzschmar HA, Zerr I
J Neurol Neurosurg Psychiatry 2014 Jun;85(6):654-9. Epub 2013 Nov 18 doi: 10.1136/jnnp-2013-305978. PMID: 24249784Free PMC Article
Rupprecht S, Grimm A, Schultze T, Zinke J, Karvouniari P, Axer H, Witte OW, Schwab M
J Clin Sleep Med 2013 Dec 15;9(12):1343-5. doi: 10.5664/jcsm.3286. PMID: 24340298Free PMC Article
Tian C, Liu D, Sun QL, Chen C, Xu Y, Wang H, Xiang W, Kretzschmar HA, Li W, Chen C, Shi Q, Gao C, Zhang J, Zhang BY, Han J, Dong XP
Mol Neurobiol 2013 Aug;48(1):36-48. Epub 2013 Feb 21 doi: 10.1007/s12035-013-8426-6. PMID: 23430483
Casas-Méndez LF, Lujan M, Vigil L, Sansa G
J Clin Sleep Med 2011 Feb 15;7(1):89-91. PMID: 21344052Free PMC Article
Krasnianski A, Bartl M, Sanchez Juan PJ, Heinemann U, Meissner B, Varges D, Schulze-Sturm U, Kretzschmar HA, Schulz-Schaeffer WJ, Zerr I
Ann Neurol 2008 May;63(5):658-61. doi: 10.1002/ana.21358. PMID: 18360821

Therapy

Forloni G, Tettamanti M, Lucca U, Albanese Y, Quaglio E, Chiesa R, Erbetta A, Villani F, Redaelli V, Tagliavini F, Artuso V, Roiter I
Prion 2015;9(2):75-9. doi: 10.1080/19336896.2015.1027857. PMID: 25996399Free PMC Article
Jackson WS, Borkowski AW, Faas H, Steele AD, King OD, Watson N, Jasanoff A, Lindquist S
Neuron 2009 Aug 27;63(4):438-50. doi: 10.1016/j.neuron.2009.07.026. PMID: 19709627Free PMC Article
Schenkein J, Montagna P
MedGenMed 2006 Sep 14;8(3):66. PMID: 17406189Free PMC Article
Schenkein J, Montagna P
MedGenMed 2006 Sep 14;8(3):65. PMID: 17406188Free PMC Article
Benito-León J
Clin Neuropharmacol 2004 Jul-Aug;27(4):201-3. PMID: 15319710

Prognosis

Peng B, Zhang S, Dong H, Lu Z
Int J Clin Exp Pathol 2015;8(9):10171-7. Epub 2015 Sep 1 PMID: 26617725Free PMC Article
Cortelli P, Fabbri M, Calandra-Buonaura G, Capellari S, Tinuper P, Parchi P, Lugaresi E
Mov Disord 2014 Mar;29(3):420-4. Epub 2013 Dec 27 doi: 10.1002/mds.25786. PMID: 24375448
Krasnianski A, Sanchez Juan P, Ponto C, Bartl M, Heinemann U, Varges D, Schulz-Schaeffer WJ, Kretzschmar HA, Zerr I
J Neurol Neurosurg Psychiatry 2014 Jun;85(6):654-9. Epub 2013 Nov 18 doi: 10.1136/jnnp-2013-305978. PMID: 24249784Free PMC Article
Rupprecht S, Grimm A, Schultze T, Zinke J, Karvouniari P, Axer H, Witte OW, Schwab M
J Clin Sleep Med 2013 Dec 15;9(12):1343-5. doi: 10.5664/jcsm.3286. PMID: 24340298Free PMC Article
Casas-Méndez LF, Lujan M, Vigil L, Sansa G
J Clin Sleep Med 2011 Feb 15;7(1):89-91. PMID: 21344052Free PMC Article

Clinical prediction guides

Tian C, Liu D, Xiang W, Kretzschmar HA, Sun QL, Gao C, Xu Y, Wang H, Fan XY, Meng G, Li W, Dong XP
Mol Neurobiol 2014 Oct;50(2):473-81. Epub 2014 Jun 7 doi: 10.1007/s12035-014-8758-x. PMID: 24902808
Krasnianski A, Sanchez Juan P, Ponto C, Bartl M, Heinemann U, Varges D, Schulz-Schaeffer WJ, Kretzschmar HA, Zerr I
J Neurol Neurosurg Psychiatry 2014 Jun;85(6):654-9. Epub 2013 Nov 18 doi: 10.1136/jnnp-2013-305978. PMID: 24249784Free PMC Article
Tian C, Liu D, Sun QL, Chen C, Xu Y, Wang H, Xiang W, Kretzschmar HA, Li W, Chen C, Shi Q, Gao C, Zhang J, Zhang BY, Han J, Dong XP
Mol Neurobiol 2013 Aug;48(1):36-48. Epub 2013 Feb 21 doi: 10.1007/s12035-013-8426-6. PMID: 23430483
Shi XH, Han J, Zhang J, Shi Q, Chen JM, Xia SL, Xie ZQ, Shen XJ, Shan B, Lei YJ, Shi S, Zhou W, Zhang BY, Gao C, Liu YH, Song J, Guo YJ, Wang DX, Xu BL, Dong XP
Infect Genet Evol 2010 Mar;10(2):292-7. Epub 2010 Jan 22 doi: 10.1016/j.meegid.2010.01.007. PMID: 20096809
Sasaki K, Doh-ura K, Wakisaka Y, Tomoda H, Iwaki T
Neuropathol Appl Neurobiol 2005 Feb;31(1):80-7. doi: 10.1111/j.1365-2990.2004.00592.x. PMID: 15634234

Recent systematic reviews

Calandra-Buonaura G, Provini F, Guaraldi P, Plazzi G, Cortelli P
Sleep Med Rev 2016 Apr;26:43-56. Epub 2015 Jun 3 doi: 10.1016/j.smrv.2015.05.005. PMID: 26146026
Capellari S, Strammiello R, Saverioni D, Kretzschmar H, Parchi P
Acta Neuropathol 2011 Jan;121(1):21-37. Epub 2010 Oct 27 doi: 10.1007/s00401-010-0760-4. PMID: 20978903

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