FFI
MCID: FTL002
MIFTS: 50

Fatal Familial Insomnia (FFI)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Fatal Familial Insomnia

MalaCards integrated aliases for Fatal Familial Insomnia:

Name: Fatal Familial Insomnia 57 12 73 73 20 58 72 29 6 15 70
Insomnia, Fatal Familial 57 13 44
Ffi 57 72
Insomnia, Fatal, Familial 39
Familial Fatal Insomnia 20
Insomnia Familial Fatal 20
Insomnia Fatal Familial 54

Characteristics:

Orphanet epidemiological data:

58
fatal familial insomnia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in adulthood
rapid course
death within 12 months


HPO:

31
fatal familial insomnia:
Inheritance autosomal dominant inheritance
Onset and clinical course adult onset childhood onset


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0050433
OMIM® 57 600072
ICD9CM 34 046.72
MeSH 44 D034062
NCIt 50 C84711
SNOMED-CT 67 83157008
ICD10 32 A81.83
MESH via Orphanet 45 D034062
ICD10 via Orphanet 33 A81.8
UMLS via Orphanet 71 C0206042
Orphanet 58 ORPHA466
MedGen 41 C0206042
UMLS 70 C0206042

Summaries for Fatal Familial Insomnia

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) (Updated 05-Apr-2021)

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 ataxia, constipation and fever. An important gene associated with Fatal Familial Insomnia is PRNP (Prion Protein), and among its related pathways/superpathways are JAK-STAT signaling pathway and Neuroscience. Affiliated tissues include brain, thalamus and cortex, and related phenotypes are diplopia and hyperhidrosis

Disease Ontology : 12 A prion disease that is characterized by insomnia, hallucinations, dementia and death, located in the brain.

GARD : 20 Fatal familial insomnia (FFI) affects the thalamus, the part of the brain that controls the sleep-wake cycle. Symptoms typically begin between the ages of 40-60 years. The most common symptoms are sleep disturbance, psychiatric problems, weight loss, and balance problems. Other symptoms include high blood pressure, excess sweating, and difficulty controlling body temperature. These symptoms tend to get worse over time. FFI is usually fatal in 6-36 months. Almost all cases of FFI occur due to a specific variant in the PRNP gene and are inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, sleep study, and imaging studies. The results of genetic testing can help confirm the diagnosis. Treatment for FFI is focused on managing the symptoms.

UniProtKB/Swiss-Prot : 72 Fatal familial insomnia: Autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.

Wikipedia : 73 Fatal insomnia is an extremely rare disorder that results in trouble sleeping as its hallmark symptom.... more...

Related Diseases for Fatal Familial Insomnia

Diseases in the Fatal Familial Insomnia family:

Sporadic Fatal Insomnia

Diseases related to Fatal Familial Insomnia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 176)
# Related Disease Score Top Affiliating Genes
1 prion disease 31.2 SPRN SNCA PRNP PRND MSMB MAPT
2 gerstmann-straussler disease 30.6 SPRN SNCA PRNP PRND MSMB MIRLET7I
3 frontotemporal lobar degeneration with tdp43 inclusions, grn-related 30.5 PRNP MAPT
4 kuru 29.9 SPRN SNCA PRNP PRND MSMB MAPT
5 sleep disorder 29.6 SNCA PRODH PER2 MAPT IL6 HCRT
6 respiratory failure 29.6 SERPINA3 MAPT IL6 HCRT
7 anxiety 29.5 SNCA PRODH IL6 HCRT APP
8 creutzfeldt-jakob disease 29.3 SPRN SNCA SERPINA3 PRNP PRND MSMB
9 movement disease 29.2 SNCA SERPINA3 PRODH MAPT HTT ERCC6
10 leukoencephalopathy, hereditary diffuse, with spheroids 29.1 SNCA PRNP MAPT GFAP APP
11 bipolar disorder 29.0 PRODH PER2 MAPT IL6 APP
12 autosomal dominant cerebellar ataxia 29.0 SNCA SERPINA3 PRNP MAPT HTT ERCC6
13 dementia 28.7 SNCA SERPINA3 PRNP MAPT HTT GFAP
14 frontotemporal dementia 28.4 SNCA PRNP MAPT HTT HCRT GFAP
15 scrapie 28.3 SPRN SNCA SERPINA3 PRNP PRND MSMB
16 amyotrophic lateral sclerosis 1 28.0 SNCA SERPINA3 PRODH PRNP MAPT IL6
17 dysautonomia 10.7
18 myoclonus 10.5
19 encephalopathy 10.4
20 ataxia and polyneuropathy, adult-onset 10.4
21 sporadic fatal insomnia 10.4
22 genetic prion disease 10.3
23 inherited human prion disease 10.3
24 voyeurism 10.3 SERPINA3 PRODH
25 cortical deafness 10.3 TXNDC9 PRNP
26 huntington disease-like 1 10.3
27 subacute delirium 10.3
28 intestinal perforation 10.3 SERPINA3 PRODH IL6
29 bone structure disease 10.2 PRODH IL6 ERCC6
30 post-transplant lymphoproliferative disease 10.2 IL6 IL10RA
31 teeth hard tissue disease 10.2 SERPINA3 IL6 ERCC6
32 mental depression 10.2 SERPINA3 PRODH IL6
33 degeneration of macula and posterior pole 10.2 SERPINA3 IL6 ERCC6
34 testicular disease 10.2 SERPINA3 IL6 ERCC6
35 lens disease 10.2 SERPINA3 IL6 ERCC6
36 gerstmann syndrome 10.2 PRNP MAPT
37 aspiration pneumonia 10.2 SNCA SERPINA3 IL6
38 prostatitis 10.2 SERPINA3 MSMB IL6
39 intestinal benign neoplasm 10.2 SERPINA3 IL6 ERCC6
40 hair disease 10.2 SERPINA3 IL6 ERCC6
41 placenta disease 10.2 SERPINA3 PRODH IL6
42 parasitic protozoa infectious disease 10.2 SERPINA3 PRODH IL6
43 fasciitis 10.2
44 plantar fasciitis 10.2
45 bone resorption disease 10.2 SERPINA3 IL6 ERCC6
46 gastrointestinal system benign neoplasm 10.2 SERPINA3 IL6 ERCC6
47 cerebral amyloid angiopathy, itm2b-related, 1 10.2 SERPINA3 PRNP APP
48 dysthymic disorder 10.2 PRODH IL6 HCRT
49 corneal disease 10.2 SERPINA3 IL6 ERCC6
50 alzheimer disease 18 10.2 SNCA APP

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



Diseases related to Fatal Familial Insomnia

Symptoms & Phenotypes for Fatal Familial Insomnia

Human phenotypes related to Fatal Familial Insomnia:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 diplopia 31 HP:0000651
2 hyperhidrosis 31 HP:0000975
3 ataxia 31 HP:0001251
4 dysarthria 31 HP:0001260
5 dysphagia 31 HP:0002015
6 constipation 31 HP:0002019
7 fever 31 HP:0001945
8 myoclonus 31 HP:0001336
9 apnea 31 HP:0002104
10 insomnia 31 HP:0100785
11 weight loss 31 HP:0001824
12 dementia 31 HP:0000726
13 urinary retention 31 HP:0000016
14 neuronal loss in central nervous system 31 HP:0002529
15 abnormal autonomic nervous system physiology 31 HP:0012332

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
ataxia
dysarthria
dysautonomia
myoclonus
dementia
more
Metabolic Features:
fever

Genitourinary Bladder:
urinary retention

Skin Nails Hair Skin:
diaphoresis

Abdomen Gastrointestinal:
dysphagia
constipation

Growth Weight:
weight loss

Head And Neck Eyes:
diplopia, intermittent

Respiratory:
apneic episodes

Clinical features from OMIM®:

600072 (Updated 05-Apr-2021)

UMLS symptoms related to Fatal Familial Insomnia:


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

MGI Mouse Phenotypes related to Fatal Familial Insomnia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.24 APP CSF3R ERCC6 GFAP HCRT HTT
2 cellular MP:0005384 10.1 APP CSF3R ERCC6 GFAP HTT IL10RA
3 homeostasis/metabolism MP:0005376 10.1 APP ERCC6 ERI3 GFAP HCRT HTT
4 immune system MP:0005387 9.93 APP CSF3R ERCC6 GFAP HTT IL10RA
5 integument MP:0010771 9.7 APP ERCC6 HTT IL6 MAPT MSMB
6 nervous system MP:0003631 9.44 APP ERCC6 GFAP HCRT HTT IL6

Drugs & Therapeutics for Fatal Familial Insomnia

Search Clinical Trials , 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

The Foundational Model of Anatomy Ontology organs/tissues related to Fatal Familial Insomnia:

19
Brain

MalaCards organs/tissues related to Fatal Familial Insomnia:

40
Thalamus, Brain, Cortex, Heart

Publications for Fatal Familial Insomnia

Articles related to Fatal Familial Insomnia:

(show top 50) (show all 451)
# Title Authors PMID Year
1
Phenotypic variability in familial prion diseases due to the D178N mutation. 6 61 57
16227536 2005
2
Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. 57 54 61
19709627 2009
3
Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200(Lys) mutation. 6 61 54
8618678 1996
4
Molecular genetic studies of Creutzfeldt-Jakob disease. 6 54 61
7999318 1994
5
Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. 54 61 57
1346338 1992
6
Discordant clinicopathologic phenotypes in a Japanese kindred of fatal familial insomnia. 61 57
20038778 2010
7
Fatal familial insomnia: Clinical features and early identification. 61 57
18360821 2008
8
Sporadic fatal insomnia in a fatal familial insomnia pedigree. 57 61
18332347 2008
9
Agrypnia excitata in fatal familial insomnia. A video-polygraphic study. 57 61
17679681 2007
10
Fatal familial insomnia presenting as psychosis in an 18-year-old man. 57 61
16864846 2006
11
Dissociation in circadian rhythms in a pseudohypersomnia form of fatal familial insomnia. 61 57
15623717 2004
12
Fatal familial insomnia: the first account in a family of Chinese descent. 57 61
14732629 2004
13
Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease. 6 61
11839833 2002
14
Sporadic fatal insomnia: a case study. 61 57
11026452 2000
15
Novel twelve-generation kindred of fatal familial insomnia from germany representing the entire spectrum of disease expression. 61 57
10588836 1999
16
A subtype of sporadic prion disease mimicking fatal familial insomnia. 57 61
10371520 1999
17
Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene. 57 61
9669701 1998
18
Altered circadian activity rhythms and sleep in mice devoid of prion protein. 61 57
8602267 1996
19
First experimental transmission of fatal familial insomnia. 57 61
7630420 1995
20
Regional distribution of protease-resistant prion protein in fatal familial insomnia. 57 61
7611720 1995
21
Codon 178 mutation of the human prion protein gene in a German family (Backer family): sequencing data from 72-year-old celloidin-embedded brain tissue. 61 6
7709737 1995
22
Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. 61 57
1439789 1992
23
Fatal familial insomnia: clinical and pathologic study of five new cases. 61 57
1736158 1992
24
Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. 57 61
3762620 1986
25
Genetic Creutzfeldt-Jakob disease. 6
29887139 2018
26
Ascertainment bias causes false signal of anticipation in genetic prion disease. 6
25279981 2014
27
Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model. 6
19038218 2008
28
Spontaneous mutations in the prion protein gene causing transmissible spongiform encephalopathy. 6
12205650 2002
29
Age and origin of the PRNP E200K mutation causing familial Creutzfeldt-Jacob disease in Libyan Jews. 6
10889050 2000
30
Creutzfeldt-Jakob disease profile in patients homozygous for the PRNP E200K mutation. 6
10665501 2000
31
Prominent psychiatric features and early onset in an inherited prion disease with a new insertional mutation in the prion protein gene. 6
10581230 1999
32
Prion protein conformation in a patient with sporadic fatal insomnia. 57
10341275 1999
33
Insomnia in prion diseases: sporadic and familial. 57
10341282 1999
34
Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease. 6
10090891 1999
35
Prion protein NMR structure and familial human spongiform encephalopathies. 6
9751723 1998
36
Familial Creutzfeldt-Jakob disease. Codon 200 prion disease in Libyan Jews. 6
9279329 1997
37
The risk of developing Creutzfeldt-Jakob disease in subjects with the PRNP gene codon 200 point mutation. 6
7936296 1994
38
Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein. 6
7916462 1994
39
Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD). 6
8105682 1993
40
Familial Creutzfeldt-Jakob disease (codon 200 mutation) with supranuclear palsy. 6
1404799 1992
41
Familial Creutzfeldt-Jakob disease in Chile is associated with the codon 200 mutation of the PRNP amyloid precursor gene on chromosome 20. 6
1469441 1992
42
Transmission of spongiform encephalopathy from a familial Creutzfeldt-Jakob disease patient of Jewish Libyan origin carrying the PRNP codon 200 mutation. 6
1351274 1992
43
Creutzfeldt-Jakob disease cosegregates with the codon 178Asn PRNP mutation in families of European origin. 6
1353341 1992
44
Phenotypic characteristics of familial Creutzfeldt-Jakob disease associated with the codon 178Asn PRNP mutation. 6
1353342 1992
45
The transmissible amyloidoses: genetical control of spontaneous generation of infectious amyloid proteins by nucleation of configurational change in host precursors: kuru-CJD-GSS-scrapie-BSE. 6
1684758 1991
46
Familial Creutzfeldt-Jakob disease in Finland: epidemiological, clinical, pathological and molecular genetic studies. 6
1684756 1991
47
Creutzfeldt-Jacob disease associated with the PRNP codon 200Lys mutation: an analysis of 45 families. 6
1684755 1991
48
Codon 178 mutation in ethnically diverse Creutzfeldt-Jakob disease families. 6
1671983 1991
49
New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred. 6
1671440 1991
50
Genetic and environmental factors determining the development of Creutzfeldt-Jakob disease in Libyan Jews. 6
1798423 1991

Variations for Fatal Familial Insomnia

ClinVar genetic disease variations for Fatal Familial Insomnia:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PRNP NM_000311.5(PRNP):c.598G>A (p.Glu200Lys) SNV Pathogenic 13398 rs28933385 GRCh37: 20:4680464-4680464
GRCh38: 20:4699818-4699818
2 PRNP NM_000311.5(PRNP):c.385A>G (p.Met129Val) SNV Pathogenic 13399 rs1799990 GRCh37: 20:4680251-4680251
GRCh38: 20:4699605-4699605
3 PRNP NM_000311.5(PRNP):c.532G>A (p.Asp178Asn) SNV Pathogenic 39359 rs74315403 GRCh37: 20:4680398-4680398
GRCh38: 20:4699752-4699752

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

72
# Symbol AA change Variation ID SNP ID
1 PRNP p.Asp178Asn VAR_006469 rs74315403

Expression for Fatal Familial Insomnia

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

Pathways for Fatal Familial Insomnia

Pathways related to Fatal Familial Insomnia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.85 IL6 IL10RA GFAP CSF3R
2 11.7 SNCA PRNP MAPT HTT HCRT GFAP
3 10.86 PRNP MAPT APP

GO Terms for Fatal Familial Insomnia

Cellular components related to Fatal Familial Insomnia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.65 SPRN SNCA SERPINA3 PRND MSMB MAPT
2 rough endoplasmic reticulum GO:0005791 9.43 SNCA HCRT APP
3 astrocyte projection GO:0097449 9.37 GFAP APP
4 glial cell projection GO:0097386 9.32 MAPT GFAP
5 main axon GO:0044304 9.16 MAPT APP
6 inclusion body GO:0016234 8.8 SNCA PRNP HTT

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 protein homooligomerization GO:0051260 9.73 PRNP PRND MAPT
2 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.69 SNCA IL6 APP
3 learning or memory GO:0007611 9.61 PRNP MAPT APP
4 synapse organization GO:0050808 9.58 SNCA MAPT APP
5 neuron projection development GO:0031175 9.56 MAPT IL6 ERCC6 APP
6 astrocyte activation GO:0048143 9.55 MAPT APP
7 negative regulation of long-term synaptic potentiation GO:1900272 9.54 PRNP APP
8 protein destabilization GO:0031648 9.54 SNCA PRNP HTT
9 supramolecular fiber organization GO:0097435 9.52 SNCA MAPT
10 positive regulation of neuron death GO:1901216 9.5 SNCA PRNP MAPT
11 amyloid fibril formation GO:1990000 9.49 MAPT APP
12 neuron projection maintenance GO:1990535 9.48 PRNP APP
13 modulation of age-related behavioral decline GO:0090647 9.46 PRNP APP
14 microglial cell activation GO:0001774 9.33 SNCA MAPT APP
15 cellular response to copper ion GO:0071280 9.13 SNCA PRNP APP
16 cellular copper ion homeostasis GO:0006878 8.8 PRNP PRND APP

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

# Name GO ID Score Top Affiliating Genes
1 dynactin binding GO:0034452 9.16 MAPT HTT
2 cuprous ion binding GO:1903136 8.96 SNCA PRNP
3 copper ion binding GO:0005507 8.8 SNCA PRNP PRND

Sources for Fatal Familial Insomnia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....