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Familial encephalopathy with neuroserpin inclusion bodies(FENIB)

MedGen UID:
346965
Concept ID:
C1858680
Disease or Syndrome
Synonym: Encephalopathy, familial, with Collins bodies
SNOMED CT: Familial encephalopathy with neuroserpin inclusion bodies (702421006); Familial dementia with neuroserpin inclusion bodies (702421006)
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.
 
Gene (location): SERPINI1 (3q26.1)
 
Monarch Initiative: MONDO:0011412
OMIM®: 604218
Orphanet: ORPHA85110

Definition

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is an autosomal dominant disorder characterized by progressive epilepsy and dementia. Onset of symptoms ranges from the second to fifth decades of life. Severity is variable (summary by Molinari et al., 2003). [from OMIM]

Additional description

From MedlinePlus Genetics
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy). It is characterized by a loss of intellectual functioning (dementia) and seizures. At first, affected individuals may have difficulty sustaining attention and concentrating. They may experience repetitive thoughts, speech, or movements. As the condition progresses, their personality changes and judgment, insight, and memory become impaired. Affected people lose the ability to perform the activities of daily living, and most eventually require comprehensive care.

The signs and symptoms of FENIB vary in their severity and age of onset. In severe cases, the condition causes seizures and episodes of sudden, involuntary muscle jerking or twitching (myoclonus) in addition to dementia. These signs can appear as early as a person's teens. Less severe cases are characterized by a progressive decline in intellectual functioning beginning in a person's forties or fifties.  https://medlineplus.gov/genetics/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies

Clinical features

From HPO
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.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
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.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Eosinophilic neuronal inclusion bodies
MedGen UID:
1053951
Concept ID:
CN378411
Finding
The presence of intracellular inclusion bodies (aggregates of stainable substances, usually proteins) in neurons that stain with eosin, a red or pink dye.
Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Disease or Syndrome
Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial encephalopathy with neuroserpin inclusion bodies
Follow this link to review classifications for Familial encephalopathy with neuroserpin inclusion bodies in Orphanet.

Recent clinical studies

Etiology

Roussel BD, Irving JA, Ekeowa UI, Belorgey D, Haq I, Ordóñez A, Kruppa AJ, Duvoix A, Rashid ST, Crowther DC, Marciniak SJ, Lomas DA
FEBS J 2011 Oct;278(20):3859-67. Epub 2011 Jun 20 doi: 10.1111/j.1742-4658.2011.08201.x. PMID: 21624056
Belorgey D, Irving JA, Ekeowa UI, Freeke J, Roussel BD, Miranda E, Pérez J, Robinson CV, Marciniak SJ, Crowther DC, Michel CH, Lomas DA
Methods 2011 Mar;53(3):255-66. Epub 2010 Nov 27 doi: 10.1016/j.ymeth.2010.11.008. PMID: 21115126
Lomas DA
Clin Med (Lond) 2005 May-Jun;5(3):249-57. doi: 10.7861/clinmedicine.5-3-249. PMID: 16011217Free PMC Article
Lomas DA, Belorgey D, Mallya M, Onda M, Kinghorn KJ, Sharp LK, Phillips RL, Page R, Crowther DC, Miranda E
Front Biosci 2004 Sep 1;9:2873-91. doi: 10.2741/1444. PMID: 15353322

Diagnosis

Handa H, Sugiyama A, Kaname T, Shigemoto Y, Sato N, Hirano S, Nakagawa Y, Uzawa A, Aotsuka A, Kuwabara S
BMC Neurol 2024 Jan 2;24(1):9. doi: 10.1186/s12883-023-03511-0. PMID: 38166833Free PMC Article
Yang X, Fang Z, Yan L, He X, Luo H, Han Z, Gui J, Cheng M, Jiang L
Seizure 2022 Dec;103:137-147. Epub 2022 Nov 13 doi: 10.1016/j.seizure.2022.11.008. PMID: 36417830
Miranda E, MacLeod I, Davies MJ, Pérez J, Römisch K, Crowther DC, Lomas DA
Hum Mol Genet 2008 Jun 1;17(11):1527-39. Epub 2008 Feb 11 doi: 10.1093/hmg/ddn041. PMID: 18267959Free PMC Article
Crowther DC, Belorgey D, Miranda E, Kinghorn KJ, Sharp LK, Lomas DA
Eur J Hum Genet 2004 Mar;12(3):167-72. doi: 10.1038/sj.ejhg.5201127. PMID: 14694355

Therapy

Takasawa A, Kato I, Takasawa K, Ishii Y, Yoshida T, Shehata MH, Kawaguchi H, Mohafez OM, Sasahara M, Hiraga K
J Biol Chem 2008 Dec 19;283(51):35606-13. Epub 2008 Oct 21 doi: 10.1074/jbc.M804125200. PMID: 18940798

Prognosis

Moriconi C, Ordoñez A, Lupo G, Gooptu B, Irving JA, Noto R, Martorana V, Manno M, Timpano V, Guadagno NA, Dalton L, Marciniak SJ, Lomas DA, Miranda E
FEBS J 2015 Dec;282(23):4565-79. Epub 2015 Oct 3 doi: 10.1111/febs.13517. PMID: 26367528Free PMC Article
Noto R, Randazzo L, Raccosta S, Caccia S, Moriconi C, Miranda E, Martorana V, Manno M
Sci Rep 2015 Sep 2;5:13666. doi: 10.1038/srep13666. PMID: 26329378Free PMC Article
Galliciotti G, Glatzel M, Kinter J, Kozlov SV, Cinelli P, Rülicke T, Sonderegger P
Am J Pathol 2007 Apr;170(4):1305-13. doi: 10.2353/ajpath.2007.060910. PMID: 17392169Free PMC Article
Belorgey D, Sharp LK, Crowther DC, Onda M, Johansson J, Lomas DA
Eur J Biochem 2004 Aug;271(16):3360-7. doi: 10.1111/j.1432-1033.2004.04270.x. PMID: 15291813
Davis RL, Shrimpton AE, Holohan PD, Bradshaw C, Feiglin D, Collins GH, Sonderegger P, Kinter J, Becker LM, Lacbawan F, Krasnewich D, Muenke M, Lawrence DA, Yerby MS, Shaw CM, Gooptu B, Elliott PR, Finch JT, Carrell RW, Lomas DA
Nature 1999 Sep 23;401(6751):376-9. doi: 10.1038/43894. PMID: 10517635

Clinical prediction guides

Yang X, Fang Z, Yan L, He X, Luo H, Han Z, Gui J, Cheng M, Jiang L
Seizure 2022 Dec;103:137-147. Epub 2022 Nov 13 doi: 10.1016/j.seizure.2022.11.008. PMID: 36417830
Ingwersen T, Linnenberg C, D'Acunto E, Temori S, Paolucci I, Wasilewski D, Mohammadi B, Kirchmair J, Glen RC, Miranda E, Glatzel M, Galliciotti G
Sci Rep 2021 Apr 22;11(1):8766. doi: 10.1038/s41598-021-88090-1. PMID: 33888787Free PMC Article
Visentin C, Broggini L, Sala BM, Russo R, Barbiroli A, Santambrogio C, Nonnis S, Dubnovitsky A, Bolognesi M, Miranda E, Achour A, Ricagno S
Int J Mol Sci 2020 May 3;21(9) doi: 10.3390/ijms21093235. PMID: 32375228Free PMC Article
Moriconi C, Ordoñez A, Lupo G, Gooptu B, Irving JA, Noto R, Martorana V, Manno M, Timpano V, Guadagno NA, Dalton L, Marciniak SJ, Lomas DA, Miranda E
FEBS J 2015 Dec;282(23):4565-79. Epub 2015 Oct 3 doi: 10.1111/febs.13517. PMID: 26367528Free PMC Article
Takano K, Kitao Y, Inagi R, Momoi T, Matsuyama T, Miyata T, Yoneda Y, Iso H, Stern DM, Hori O, Ogawa S
Biochem Biophys Res Commun 2006 Aug 4;346(3):1040-7. Epub 2006 Jun 12 doi: 10.1016/j.bbrc.2006.06.016. PMID: 16782060

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