MCID: FTL002
MIFTS: 49

Fatal Familial Insomnia

Categories: Genetic diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Fatal Familial Insomnia

MalaCards integrated aliases for Fatal Familial Insomnia:

Name: Fatal Familial Insomnia 57 12 76 53 59 75 29 6 15 73
Insomnia, Fatal Familial 57 13 44
Ffi 57 75
Insomnia, Fatal, Familial 40
Familial Fatal Insomnia 53
Insomnia Familial Fatal 53
Insomnia Fatal Familial 55

Characteristics:

Orphanet epidemiological data:

59
fatal familial insomnia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset in adulthood
rapid course
death within 12 months


HPO:

32
fatal familial insomnia:
Onset and clinical course adult onset childhood onset
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Fatal Familial Insomnia

NIH Rare Diseases : 53 Fatal familial insomnia (FFI) is an inherited prion disease that mainly affects the thalamus. The thalamus is the part of the brain that controls the sleep-wake cycle, but is also known as the "relay center" of the brain because it helps the different parts of the brain communicate with each other. Like all prion diseases, FFI is a progressive neurodegenerative disease, which means over time there are fewer neurons (nerve cells). Loss of neurons in the thalamus, as well as other mechanisms not yet fully understood, cause the symptoms of FFI.  The first symptoms of FFI usually begin in mid-life and may include progressive insomnia, weight loss, lack of appetite, too high or too low body temperature, and rapidly progressive dementia. Almost all cases of FFI are caused by certain changes (mutations) in the PRNP gene and are inherited in an autosomal dominant manner. There are a very small number of reported sporadic cases of FFI. There is currently no effective treatment for FFI, but research for a treatment and cure is ongoing. Death usually occurs within 12-18 months of the first symptoms.

MalaCards based summary : Fatal Familial Insomnia, also known as insomnia, fatal familial, is related to prion disease and gerstmann-straussler disease, and has symptoms including apnea, ataxia and constipation. An important gene associated with Fatal Familial Insomnia is PRNP (Prion Protein), and among its related pathways/superpathways are Cytokine Signaling in Immune system and Regulation of IFNA signaling. The drugs Formaldehyde and Epinephrine have been mentioned in the context of this disorder. Affiliated tissues include thalamus, brain and cortex, and related phenotypes are urinary retention and diplopia

OMIM : 57 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). (600072)

UniProtKB/Swiss-Prot : 75 Fatal familial insomnia: Autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.

Wikipedia : 76 Fatal insomnia is an extremely rare sleep disorder which is typically inherited and results in death... more...

Related Diseases for Fatal Familial Insomnia

Graphical network of the top 20 diseases related to Fatal Familial Insomnia:



Diseases related to Fatal Familial Insomnia

Symptoms & Phenotypes for Fatal Familial Insomnia

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
ataxia
dysarthria
dysautonomia
myoclonus
dementia
more
Metabolic Features:
fever

Genitourinary Bladder:
urinary retention

Head And Neck Eyes:
diplopia, intermittent

Abdomen Gastrointestinal:
dysphagia
constipation

Growth Weight:
weight loss

Skin Nails Hair Skin:
diaphoresis

Respiratory:
apneic episodes


Clinical features from OMIM:

600072

Human phenotypes related to Fatal Familial Insomnia:

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 urinary retention 32 HP:0000016
2 diplopia 32 HP:0000651
3 dementia 32 HP:0000726
4 hyperhidrosis 32 HP:0000975
5 ataxia 32 HP:0001251
6 dysarthria 32 HP:0001260
7 myoclonus 32 HP:0001336
8 weight loss 32 HP:0001824
9 fever 32 HP:0001945
10 dysphagia 32 HP:0002015
11 constipation 32 HP:0002019
12 apnea 32 HP:0002104
13 dysautonomia 32 HP:0002459
14 neuronal loss in central nervous system 32 HP:0002529
15 insomnia 32 HP:0100785

UMLS symptoms related to Fatal Familial Insomnia:


apnea, ataxia, constipation, fever, myoclonus, increased sweating, diplopia, intermittent, sleeplessness

Drugs & Therapeutics for Fatal Familial Insomnia

Drugs for Fatal Familial Insomnia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Formaldehyde Approved, Vet_approved Phase 4 50-00-0 712
2
Epinephrine Approved, Vet_approved Phase 4 51-43-4 5816
3
Racepinephrine Approved Phase 4 329-65-7 838
4 Vasoconstrictor Agents Phase 4
5 Epinephryl borate Phase 4
6 Pharmaceutical Solutions Phase 4
7
Quinacrine Approved, Investigational Phase 2,Not Applicable 83-89-6 237
8
Coal tar Approved Phase 2 8007-45-2
9 Anthelmintics Phase 2,Not Applicable
10 Anti-Infective Agents Phase 2,Not Applicable
11 Antiparasitic Agents Phase 2,Not Applicable
12 Antiprotozoal Agents Phase 2,Not Applicable
13 Antimalarials Phase 2,Not Applicable
14
Thrombin Approved, Investigational
15 Antibodies
16 Immunoglobulins
17 Coagulants
18 Hemostatics

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 SOLFAMU Study of Nasal Brushing Collected OLFActory MUcosa Samples in the Diagnosis of Human Encephalopathies Recruiting NCT02951559 Phase 4
2 CJD (Creutzfeldt-Jakob Disease) Quinacrine Study Completed NCT00183092 Phase 2 Quinacrine;Placebo
3 A Trial to Investigate the Relative Efficacy, Safety, and Tolerability of Octaplas LG Versus Octaplas SD Completed NCT01063595 Phase 1
4 Notification of Donors With Positive Microbiology Markers Unknown status NCT01050881
5 The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH) Completed NCT00721864
6 PRION-1: Quinacrine for Human Prion Disease Completed NCT00104663 Not Applicable Quinacrine
7 Therapeutic Antibodies Against Prion Diseases From PRNP Mutation Carriers Recruiting NCT02837705
8 Enhanced CJD Surveillance in the Older Population Recruiting NCT02629640
9 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
10 The Role of the Coagulation Pathway at the Synapse in Prion Diseases Not yet recruiting NCT02480725

Search NIH Clinical Center for Fatal Familial Insomnia

Cochrane evidence based reviews: insomnia, fatal familial

Genetic Tests for Fatal Familial Insomnia

Genetic tests related to Fatal Familial Insomnia:

# Genetic test Affiliating Genes
1 Fatal Familial Insomnia 29 PRNP

Anatomical Context for Fatal Familial Insomnia

MalaCards organs/tissues related to Fatal Familial Insomnia:

41
Thalamus, Brain, Cortex

Publications for Fatal Familial Insomnia

Articles related to Fatal Familial Insomnia:

(show top 50) (show all 127)
# Title Authors Year
1
An inA vivo<sup>11</sup>C-PK PET study of microglia activation in Fatal Familial Insomnia. ( 29376088 )
2018
2
Fatal familial insomnia presenting with agrypnia excitata and very low atonia index level: A case report and literature review. ( 29718878 )
2018
3
18F-FDG PET Brain in a Patient With Fatal Familial Insomnia. ( 29877883 )
2018
4
Fatal familial insomnia and sporadic fatal insomnia. ( 29887141 )
2018
5
Expert Consensus on Clinical Diagnostic Criteria for Fatal Familial Insomnia. ( 29941716 )
2018
6
A Case of Fatal Familial Insomnia Initially Developing Parkinsonism Mimicking Dementia with Lewy Bodies. ( 29709939 )
2018
7
Detection of prion seeding activity in the olfactory mucosa of patients with Fatal Familial Insomnia. ( 28387370 )
2017
8
Clinical and neuroimaging features of a Chinese patient with fatal familial insomnia. ( 28057496 )
2017
9
Fatal familial insomnia: mitochondrial and protein synthesis machinery decline in the mediodorsal thalamus. ( 27338255 )
2017
10
Fatal familial insomnia with abnormal signals on routine MRI: a case report and literature review. ( 28549449 )
2017
11
Losing sleep over mitochondria: a new player in the pathophysiology of fatal familial insomnia. ( 27350067 )
2017
12
Genetic and Rare Disease of the CNS. Part I: Fatal Familial Insomnia (FFI). ( 29258312 )
2017
13
Agrypnia excitata and obstructive apnea in a patient with fatal familial insomnia from China: A case report. ( 29245265 )
2017
14
Fatal Familial Insomnia: Clinical Aspects and Molecular Alterations. ( 28324299 )
2017
15
Fatal familial insomnia: a video-polysomnographic case report. ( 28449898 )
2017
16
Clinical Features and Sleep Analysis of Chinese Patients with Fatal Familial Insomnia. ( 28620158 )
2017
17
Identification of new molecular alterations in fatal familial insomnia. ( 27056979 )
2016
18
Sexual disinhibition and agrypnia excitata in fatal familial insomnia. ( 27423578 )
2016
19
Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease. ( 25880443 )
2015
20
Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare diseases. ( 25996399 )
2015
21
Correction: Transgenic Fatal Familial Insomnia Mice Indicate Prion Infectivity-Independent Mechanisms of Pathogenesis and Phenotypic Expression of Disease. ( 26147885 )
2015
22
Clinical, histopathological and genetic studies in a case of fatal familial insomnia with review of the literature. ( 26617725 )
2015
23
Analyses of the similarity and difference of global gene expression profiles in cortex regions of three neurodegenerative diseases: sporadic Creutzfeldt-Jakob disease (sCJD), fatal familial insomnia (FFI), and Alzheimer's disease (AD). ( 24902808 )
2014
24
Midbrain hypometabolism in fatal familial insomnia: a case report and a statistical parametric mapping analysis of a korean family. ( 25473397 )
2014
25
Gait disorders in fatal familial insomnia. ( 24375448 )
2013
26
Does the clinical phenotype of fatal familial insomnia depend on PRNP codon 129 methionine-valine polymorphism? ( 24340298 )
2013
27
Comparison of the pathologic and pathogenic features in six different regions of postmortem brains of three patients with fatal familial insomnia. ( 23175354 )
2013
28
Fatal Familial Insomnia (FFI) Complicated by Posterior Reversible Encephalopathy Syndrome (PRES). ( 24141307 )
2013
29
Complex movement disorders in fatal familial insomnia: a clinical and genetic discussion. ( 23946305 )
2013
30
Brain microglia were activated in sporadic CJD but almost unchanged in fatal familial insomnia and G114V genetic CJD. ( 23816234 )
2013
31
Comparative analysis of gene expression profiles between cortex and thalamus in Chinese fatal familial insomnia patients. ( 23430483 )
2013
32
A proposal of new diagnostic pathway for fatal familial insomnia. ( 24249784 )
2013
33
Agomelatine improves sleep in a patient with fatal familial insomnia. ( 21979926 )
2012
34
Thalamic contribution to Sleep Slow Oscillation features in humans: a single case cross sectional EEG study in Fatal Familial Insomnia. ( 22609023 )
2012
35
Biot's breathing in a woman with fatal familial insomnia: is there a role for noninvasive ventilation? ( 21344052 )
2011
36
Fatal familial insomnia and the role of the thalamus in sleep regulation. ( 21056239 )
2011
37
The first case of fatal familial insomnia (FFI) in the Netherlands: a patient from Egyptian descent with concurrent four repeat tau deposits. ( 20874730 )
2011
38
Genetic Creutzfeldt-Jakob disease and fatal familial insomnia: insights into phenotypic variability and disease pathogenesis. ( 20978903 )
2011
39
Fatal familial insomnia: a middle-age-onset Chinese family kindred. ( 20133192 )
2010
40
Clinical, histopathological and genetic studies in a family with fatal familial insomnia. ( 20096809 )
2010
41
Discordant clinicopathologic phenotypes in a Japanese kindred of fatal familial insomnia. ( 20038778 )
2010
42
[Studies on heredity rule of the first genealogy regarding fatal familial insomnia in Henan province]. ( 19565837 )
2009
43
A case of fatal familial insomnia in Africa. ( 19526349 )
2009
44
Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. ( 19709627 )
2009
45
The behavioural features of fatal familial insomnia: A new Italian case with pathological verification. ( 18824410 )
2009
46
Insulin resistance to both glucose and aminoacid metabolism in a patient with Fatal Familial Insomnia. ( 18799296 )
2008
47
Fatal familial insomnia: Clinical features and early identification. ( 18360821 )
2008
48
Global distribution of fatal familial insomnia: founder or recurrent mutations. ( 18568368 )
2008
49
Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutation. ( 18347820 )
2008
50
Sporadic fatal insomnia in a fatal familial insomnia pedigree. ( 18332347 )
2008

Variations for Fatal Familial Insomnia

UniProtKB/Swiss-Prot genetic disease variations for Fatal Familial Insomnia:

75
# Symbol AA change Variation ID SNP ID
1 PRNP p.Asp178Asn VAR_006469 rs74315403

ClinVar genetic disease variations for Fatal Familial Insomnia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PRNP NM_000311.4(PRNP): c.598G> A (p.Glu200Lys) single nucleotide variant Pathogenic rs28933385 GRCh37 Chromosome 20, 4680464: 4680464
2 PRNP NM_000311.4(PRNP): c.598G> A (p.Glu200Lys) single nucleotide variant Pathogenic rs28933385 GRCh38 Chromosome 20, 4699818: 4699818
3 PRNP NM_000311.4(PRNP): c.532G> A (p.Asp178Asn) single nucleotide variant Pathogenic rs74315403 GRCh37 Chromosome 20, 4680398: 4680398
4 PRNP NM_000311.4(PRNP): c.532G> A (p.Asp178Asn) single nucleotide variant Pathogenic rs74315403 GRCh38 Chromosome 20, 4699752: 4699752

Expression for Fatal Familial Insomnia

Search GEO for disease gene expression data for Fatal Familial Insomnia.

Pathways for Fatal Familial Insomnia

GO Terms for Fatal Familial Insomnia

Biological processes related to Fatal Familial Insomnia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 8.96 IL6 PRNP
2 cytokine-mediated signaling pathway GO:0019221 8.8 CSF3R IL10RA IL6

Molecular functions related to Fatal Familial Insomnia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine receptor activity GO:0004896 8.96 CSF3R IL10RA
2 signaling receptor activity GO:0038023 8.8 CSF3R IL10RA PRNP

Sources for Fatal Familial Insomnia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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