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Inherited Creutzfeldt-Jakob disease

MedGen UID:
155837
Concept ID:
C0751254
Disease or Syndrome
Synonym: Creutzfeldt-Jakob Disease, Familial
SNOMED CT: Familial Creutzfeldt-Jakob (715807002); fCJD (Familial Creutzfeldt-Jakob disease) (715807002); Inherited Creutzfeldt-Jakob disease (715807002)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
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.
 
Genes (locations): HLA-DQB1 (6p21.32); PRNP (20p13)
 
Monarch Initiative: MONDO:0007403
OMIM®: 123400
Orphanet: ORPHA282166

Disease characteristics

Excerpted from the GeneReview: Genetic Prion Disease
Genetic prion disease generally manifests 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. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes 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 typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome. [from GeneReviews]
Authors:
Inga Zerr  |  Matthias Schmitz   view full author information

Additional description

From OMIM
The human prion diseases occur in inherited, acquired, and sporadic forms. Approximately 15% are inherited and associated with coding mutations in the PRNP gene. Acquired prion diseases include iatrogenic CJD, kuru (245300), variant CJD (vCJD) in humans, scrapie in sheep, and bovine spongiform encephalopathy (BSE) in cattle. Variant CJD is believed to be acquired from cattle infected with BSE. However, the majority of human cases of prion disease occur as sporadic CJD (sCJD) (Collinge et al., 1996; Parchi et al., 2000; Hill et al., 2003). Johnson and Gibbs (1998) provided a comprehensive review of Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. Tyler (2003) described the characteristics of sporadic CJD as encapsulated by C. Miller Fisher in 1960.  http://www.omim.org/entry/123400

Clinical features

From HPO
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Aphasia
MedGen UID:
8159
Concept ID:
C0003537
Mental or Behavioral Dysfunction
An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write.
Confusion
MedGen UID:
3587
Concept ID:
C0009676
Mental or Behavioral Dysfunction
Lack of clarity and coherence of thought, perception, understanding, or action.
Delusion
MedGen UID:
3715
Concept ID:
C0011253
Mental or Behavioral Dysfunction
A delusion is a fixed false belief held despite evidence to the contrary. The term delusion broadly encompasses all false judgments that possess the following external characteristics to a significant, albeit unspecified, extent
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Hallucinations
MedGen UID:
6709
Concept ID:
C0018524
Mental or Behavioral Dysfunction
Perceptions in a conscious and awake state that, in the absence of external stimuli, have qualities of real perception. These perceptions are vivid, substantial, and located in external objective space.
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Apathy
MedGen UID:
39083
Concept ID:
C0085632
Mental or Behavioral Dysfunction
Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy.
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Increased CSF protein concentration
MedGen UID:
329971
Concept ID:
C1806780
Finding
Increased concentration of protein in the cerebrospinal fluid.
Extrapyramidal muscular rigidity
MedGen UID:
343817
Concept ID:
C1852470
Finding
Muscular rigidity (continuous contraction of muscles with constant resistance to passive movement).
Abnormal cerebellum morphology
MedGen UID:
400925
Concept ID:
C1866129
Anatomical Abnormality
Any structural abnormality of the cerebellum.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Loss of facial expression
MedGen UID:
343819
Concept ID:
C1852476
Finding
Supranuclear gaze palsy
MedGen UID:
314030
Concept ID:
C1720037
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a particular direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Appleby BS, Yobs DR
Handb Clin Neurol 2018;153:399-408. doi: 10.1016/B978-0-444-63945-5.00021-0. PMID: 29887147
Gaudino S, Gangemi E, Colantonio R, Botto A, Ruberto E, Calandrelli R, Martucci M, Vita MG, Masullo C, Cerase A, Colosimo C
Radiol Med 2017 May;122(5):369-385. Epub 2017 Jan 21 doi: 10.1007/s11547-017-0725-y. PMID: 28110369
Fragoso DC, Gonçalves Filho AL, Pacheco FT, Barros BR, Aguiar Littig I, Nunes RH, Maia Júnior AC, da Rocha AJ
Radiographics 2017 Jan-Feb;37(1):234-257. doi: 10.1148/rg.2017160075. PMID: 28076012

Recent clinical studies

Etiology

Canas LS, Sudre CH, De Vita E, Nihat A, Mok TH, Slattery CF, Paterson RW, Foulkes AJM, Hyare H, Cardoso MJ, Thornton J, Schott JM, Barkhof F, Collinge J, Ourselin S, Mead S, Modat M
Neuroimage Clin 2019;24:102051. Epub 2019 Oct 25 doi: 10.1016/j.nicl.2019.102051. PMID: 31734530Free PMC Article
Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG, Groveman BR, Fiorini M, Pocchiari M, Monaco S, Caughey B, Zanusso G
N Engl J Med 2014 Aug 7;371(6):519-29. doi: 10.1056/NEJMoa1315200. PMID: 25099576Free PMC Article
Collinge J, Poulter M, Davis MB, Baraitser M, Owen F, Crow TJ, Harding AE
Am J Hum Genet 1991 Dec;49(6):1351-4. PMID: 1684089Free PMC Article

Diagnosis

Canas LS, Sudre CH, De Vita E, Nihat A, Mok TH, Slattery CF, Paterson RW, Foulkes AJM, Hyare H, Cardoso MJ, Thornton J, Schott JM, Barkhof F, Collinge J, Ourselin S, Mead S, Modat M
Neuroimage Clin 2019;24:102051. Epub 2019 Oct 25 doi: 10.1016/j.nicl.2019.102051. PMID: 31734530Free PMC Article
Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG, Groveman BR, Fiorini M, Pocchiari M, Monaco S, Caughey B, Zanusso G
N Engl J Med 2014 Aug 7;371(6):519-29. doi: 10.1056/NEJMoa1315200. PMID: 25099576Free PMC Article
Nicholl D, Windl O, de Silva R, Sawcer S, Dempster M, Ironside JW, Estibeiro JP, Yuill GM, Lathe R, Will RG
J Neurol Neurosurg Psychiatry 1995 Jan;58(1):65-9. doi: 10.1136/jnnp.58.1.65. PMID: 7823070Free PMC Article
Collinge J, Poulter M, Davis MB, Baraitser M, Owen F, Crow TJ, Harding AE
Am J Hum Genet 1991 Dec;49(6):1351-4. PMID: 1684089Free PMC Article

Therapy

Bizat N, Parrales V, Laoues S, Normant S, Levavasseur E, Roussel J, Privat N, Gougerot A, Ravassard P, Beaudry P, Brandel JP, Laplanche JL, Haïk S
Brain 2021 Oct 22;144(9):2745-2758. doi: 10.1093/brain/awab152. PMID: 34687213

Prognosis

Canas LS, Sudre CH, De Vita E, Nihat A, Mok TH, Slattery CF, Paterson RW, Foulkes AJM, Hyare H, Cardoso MJ, Thornton J, Schott JM, Barkhof F, Collinge J, Ourselin S, Mead S, Modat M
Neuroimage Clin 2019;24:102051. Epub 2019 Oct 25 doi: 10.1016/j.nicl.2019.102051. PMID: 31734530Free PMC Article
Collinge J, Poulter M, Davis MB, Baraitser M, Owen F, Crow TJ, Harding AE
Am J Hum Genet 1991 Dec;49(6):1351-4. PMID: 1684089Free PMC Article

Clinical prediction guides

Canas LS, Sudre CH, De Vita E, Nihat A, Mok TH, Slattery CF, Paterson RW, Foulkes AJM, Hyare H, Cardoso MJ, Thornton J, Schott JM, Barkhof F, Collinge J, Ourselin S, Mead S, Modat M
Neuroimage Clin 2019;24:102051. Epub 2019 Oct 25 doi: 10.1016/j.nicl.2019.102051. PMID: 31734530Free PMC Article
Ghoshal N, Cali I, Perrin RJ, Josephson SA, Sun N, Gambetti P, Morris JC
Arch Neurol 2009 Oct;66(10):1240-6. doi: 10.1001/archneurol.2009.224. PMID: 19822779Free PMC Article
Collinge J, Poulter M, Davis MB, Baraitser M, Owen F, Crow TJ, Harding AE
Am J Hum Genet 1991 Dec;49(6):1351-4. PMID: 1684089Free PMC Article

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