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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: 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
MedGen UID:
892334
Concept ID:
CN000007
Functional Concept
Source: HPO
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
not inherited
MedGen UID:
832438
Concept ID:
CN227390
Intellectual Product
Source: Orphanet
Describes a disorder that is not inherited.
not inherited (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

Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Finding
Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
Constipation
MedGen UID:
368096
Concept ID:
C1963087
Finding
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Disorder of autonomic nervous system
MedGen UID:
218837
Concept ID:
C1145628
Disease or Syndrome
Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart and the widening or narrowing of your blood vessels. When something goes wrong in this system, it can cause serious problems, including. - Blood pressure problems. - Heart problems. - Trouble with breathing and swallowing. - Erectile dysfunction in men. Autonomic nervous system disorders can occur alone or as the result of another disease, such as Parkinson's disease, alcoholism and diabetes. Problems can affect either part of the system, as in complex regional pain syndromes, or all of the system. Some types are temporary, but many worsen over time. When they affect your breathing or heart function, these disorders can be life-threatening. Some autonomic nervous system disorders get better when an underlying disease is treated. Often, however, there is no cure. In that case, the goal of treatment is to improve symptoms. . NIH: National Institute of Neurological Disorders and Stroke.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Insomnia
MedGen UID:
409589
Concept ID:
C1963237
Pathologic Function
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Myoclonus
MedGen UID:
504806
Concept ID:
CN001224
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
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.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
Constipation
MedGen UID:
368096
Concept ID:
C1963087
Finding
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.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating).

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. [Epub ahead of print] PMID: 24902808
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. [Epub ahead of print] PMID: 23430483
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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 20978903

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. [Epub ahead of print] 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. [Epub ahead of print] 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
Bär KJ, Häger F, Nenadic I, Opfermann T, Brodhun M, Tauber RF, Patt S, Schulz-Schaeffer W, Gottschild D, Sauer H
Arch Neurol 2002 Nov;59(11):1815-8. PMID: 12433271

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

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. [Epub ahead of print] 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. [Epub ahead of print] 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
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. [Epub ahead of print] PMID: 22609023
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. [Epub ahead of print] 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. [Epub ahead of print] 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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 20096809
Medori R, Tritschler HJ, LeBlanc A, Villare F, Manetto V, Chen HY, Xue R, Leal S, Montagna P, Cortelli P
N Engl J Med 1992 Feb 13;326(7):444-9. doi: 10.1056/NEJM199202133260704. PMID: 1346338

Recent systematic reviews

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. [Epub ahead of print] PMID: 20978903

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