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Leukoencephalopathy with vanishing white matter 3(VWM3)

MedGen UID:
1841041
•Concept ID:
C5830405
•
Disease or Syndrome
Synonyms: Leukoencephalopathy with vanishing white matter 3, with or without ovarian failure; VWM3
 
Gene (location): EIF2B3 (1p34.1)
 
Monarch Initiative: MONDO:0957871
OMIM®: 620313

Definition

Leukoencephalopathy with vanishing white matter-3 (VWM3) is an autosomal recessive leukoencephalopathy characterized by progressive cerebellar ataxia, spasticity, and mental decline. The course is chronic and progressive, with episodes of rapid deterioration following minor head trauma. Affected females may have amenorrhea. Magnetic resonance imaging (MRI) reveals diffuse leukoencephalopathy with lesions having cerebrospinal fluid (CSF)-like signals (summary by Matsukawa et al., 2011). For a discussion of genetic heterogeneity of VWM, see 603896. [from OMIM]

Clinical features

From HPO
Secondary amenorrhea
MedGen UID:
115919
•Concept ID:
C0232940
•
Disease or Syndrome
The cessation of menstruation for six months or more in a female that is not pregnant, breastfeeding or menopausal.
See: Feature record | Search on this feature
Lower limb muscle weakness
MedGen UID:
324478
•Concept ID:
C1836296
•
Finding
Weakness of the muscles of the legs.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Leukoencephalopathy
MedGen UID:
78722
•Concept ID:
C0270612
•
Disease or Syndrome
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
See: Feature record | Search on this feature
Loss of ambulation
MedGen UID:
332305
•Concept ID:
C1836843
•
Finding
Inability to walk in a person who previous had the ability to walk.
See: Feature record | Search on this feature
Hemianopia
MedGen UID:
9193
•Concept ID:
C0018979
•
Finding
Partial or complete loss of vision in one half of the visual field of one or both eyes.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Posterior reversible encephalopathy syndrome (PRES): diagnosis and management.
Triplett JD, Kutlubaev MA, Kermode AG, Hardy T
Pract Neurol 2022 Jun;22(3):183-189. Epub 2022 Jan 19 doi: 10.1136/practneurol-2021-003194. PMID: 35046115
Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.
Wang CX
Paediatr Drugs 2021 May;23(3):213-221. Epub 2021 Apr 8 doi: 10.1007/s40272-021-00441-7. PMID: 33830467Free PMC Article
Monoclonal Gammopathy-Associated Peripheral Neuropathy: Diagnosis and Management.
Chaudhry HM, Mauermann ML, Rajkumar SV
Mayo Clin Proc 2017 May;92(5):838-850. doi: 10.1016/j.mayocp.2017.02.003. PMID: 28473042Free PMC Article

Recent clinical studies

Etiology

Progressive Multifocal Leukoencephalopathy: Pathogenesis, Diagnostic Tools, and Potential Biomarkers of Response to Therapy.
Schweitzer F, Laurent S, Cortese I, Fink GR, Silling S, Skripuletz T, Metz I, Wattjes MP, Warnke C
Neurology 2023 Oct 17;101(16):700-713. Epub 2023 Jul 24 doi: 10.1212/WNL.0000000000207622. PMID: 37487750Free PMC Article
Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis.
Debette S, Schilling S, Duperron MG, Larsson SC, Markus HS
JAMA Neurol 2019 Jan 1;76(1):81-94. doi: 10.1001/jamaneurol.2018.3122. PMID: 30422209Free PMC Article
Vanishing white matter: a leukodystrophy due to astrocytic dysfunction.
Bugiani M, Vuong C, Breur M, van der Knaap MS
Brain Pathol 2018 May;28(3):408-421. doi: 10.1111/bpa.12606. PMID: 29740943Free PMC Article
Vascular Cognitive Impairment.
Dichgans M, Leys D
Circ Res 2017 Feb 3;120(3):573-591. doi: 10.1161/CIRCRESAHA.116.308426. PMID: 28154105
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, Krull KR, Inaba H, Rubnitz JE, Metzger ML, Howard SC, Ribeiro RC, Cheng C, Reddick WE, Jeha S, Sandlund JT, Evans WE, Pui CH, Relling MV
J Clin Oncol 2014 Mar 20;32(9):949-59. Epub 2014 Feb 18 doi: 10.1200/JCO.2013.53.0808. PMID: 24550419Free PMC Article

Diagnosis

Acute disseminated encephalomyelitis.
Clare E
JAAPA 2022 Sep 1;35(9):32-35. doi: 10.1097/01.JAA.0000832604.33045.9d. PMID: 36007116
Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.
Wang CX
Paediatr Drugs 2021 May;23(3):213-221. Epub 2021 Apr 8 doi: 10.1007/s40272-021-00441-7. PMID: 33830467Free PMC Article
Vanishing white matter disease with different faces.
Güngör G, Güngör O, Çakmaklı S, Maraş Genç H, İnce H, Yeşil G, Dilber C, Aydın K
Childs Nerv Syst 2020 Feb;36(2):353-361. Epub 2019 Aug 5 doi: 10.1007/s00381-019-04334-6. PMID: 31385086
Inherited leukoencephalopathies.
Renaud DL
Semin Neurol 2012 Feb;32(1):3-8. Epub 2012 Mar 15 doi: 10.1055/s-0032-1306380. PMID: 22422201
Toxic leukoencephalopathies.
Tormoehlen LM
Neurol Clin 2011 Aug;29(3):591-605. doi: 10.1016/j.ncl.2011.05.005. PMID: 21803212

Therapy

Posterior reversible encephalopathy syndrome (PRES): diagnosis and management.
Triplett JD, Kutlubaev MA, Kermode AG, Hardy T
Pract Neurol 2022 Jun;22(3):183-189. Epub 2022 Jan 19 doi: 10.1136/practneurol-2021-003194. PMID: 35046115
Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.
Mühlbauer V, Möhler R, Dichter MN, Zuidema SU, Köpke S, Luijendijk HJ
Cochrane Database Syst Rev 2021 Dec 17;12(12):CD013304. doi: 10.1002/14651858.CD013304.pub2. PMID: 34918337Free PMC Article
Cannabinoids for the treatment of dementia.
Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L
Cochrane Database Syst Rev 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2. PMID: 34532852Free PMC Article
Memantine for dementia.
McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, Maayan N, Ware J, Debarros J
Cochrane Database Syst Rev 2019 Mar 20;3(3):CD003154. doi: 10.1002/14651858.CD003154.pub6. PMID: 30891742Free PMC Article
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, Krull KR, Inaba H, Rubnitz JE, Metzger ML, Howard SC, Ribeiro RC, Cheng C, Reddick WE, Jeha S, Sandlund JT, Evans WE, Pui CH, Relling MV
J Clin Oncol 2014 Mar 20;32(9):949-59. Epub 2014 Feb 18 doi: 10.1200/JCO.2013.53.0808. PMID: 24550419Free PMC Article

Prognosis

Acute disseminated encephalomyelitis.
Clare E
JAAPA 2022 Sep 1;35(9):32-35. doi: 10.1097/01.JAA.0000832604.33045.9d. PMID: 36007116
Volume of White Matter Hyperintensities, and Cerebral Micro-Bleeds.
Balestrieri A, Lucatelli P, Suri HS, Montisci R, Suri JS, Wintermark M, Serra A, Cheng X, Jinliang C, Sanfilippo R, Saba L
J Stroke Cerebrovasc Dis 2021 Aug;30(8):105905. Epub 2021 Jun 6 doi: 10.1016/j.jstrokecerebrovasdis.2021.105905. PMID: 34107418
Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.
Wang CX
Paediatr Drugs 2021 May;23(3):213-221. Epub 2021 Apr 8 doi: 10.1007/s40272-021-00441-7. PMID: 33830467Free PMC Article
White matter hyperintensities, cognitive impairment and dementia: an update.
Prins ND, Scheltens P
Nat Rev Neurol 2015 Mar;11(3):157-65. Epub 2015 Feb 17 doi: 10.1038/nrneurol.2015.10. PMID: 25686760
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, Krull KR, Inaba H, Rubnitz JE, Metzger ML, Howard SC, Ribeiro RC, Cheng C, Reddick WE, Jeha S, Sandlund JT, Evans WE, Pui CH, Relling MV
J Clin Oncol 2014 Mar 20;32(9):949-59. Epub 2014 Feb 18 doi: 10.1200/JCO.2013.53.0808. PMID: 24550419Free PMC Article

Clinical prediction guides

Progressive Multifocal Leukoencephalopathy: Pathogenesis, Diagnostic Tools, and Potential Biomarkers of Response to Therapy.
Schweitzer F, Laurent S, Cortese I, Fink GR, Silling S, Skripuletz T, Metz I, Wattjes MP, Warnke C
Neurology 2023 Oct 17;101(16):700-713. Epub 2023 Jul 24 doi: 10.1212/WNL.0000000000207622. PMID: 37487750Free PMC Article
Volume of White Matter Hyperintensities, and Cerebral Micro-Bleeds.
Balestrieri A, Lucatelli P, Suri HS, Montisci R, Suri JS, Wintermark M, Serra A, Cheng X, Jinliang C, Sanfilippo R, Saba L
J Stroke Cerebrovasc Dis 2021 Aug;30(8):105905. Epub 2021 Jun 6 doi: 10.1016/j.jstrokecerebrovasdis.2021.105905. PMID: 34107418
Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum.
Crow YJ, Marshall H, Rice GI, Seabra L, Jenkinson EM, Baranano K, Battini R, Berger A, Blair E, Blauwblomme T, Bolduc F, Boddaert N, Buckard J, Burnett H, Calvert S, Caumes R, Ng AC, Chiang D, Clifford DB, Cordelli DM, de Burca A, Demic N, Desguerre I, De Waele L, Di Fonzo A, Dunham SR, Dyack S, Elmslie F, Ferrand M, Fisher G, Karimiani EG, Ghoumid J, Gibbon F, Goel H, Hilmarsen HT, Hughes I, Jacob A, Jones EA, Kumar R, Leventer RJ, MacDonald S, Maroofian R, Mehta SG, Metz I, Monfrini E, Neumann D, Noetzel M, O'Driscoll M, Õunap K, Panzer A, Parikh S, Prabhakar P, Ramond F, Sandford R, Saneto R, Soh C, Stutterd CA, Subramanian GM, Talbot K, Thomas RH, Toro C, Touraine R, Wakeling E, Wassmer E, Whitney A, Livingston JH, O'Keefe RT, Badrock AP
Am J Med Genet A 2021 Jan;185(1):15-25. Epub 2020 Oct 7 doi: 10.1002/ajmg.a.61907. PMID: 33029936
Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis.
Debette S, Schilling S, Duperron MG, Larsson SC, Markus HS
JAMA Neurol 2019 Jan 1;76(1):81-94. doi: 10.1001/jamaneurol.2018.3122. PMID: 30422209Free PMC Article
Natural History of Vanishing White Matter.
Hamilton EMC, van der Lei HDW, Vermeulen G, Gerver JAM, Lourenço CM, Naidu S, Mierzewska H, Gemke RJBJ, de Vet HCW, Uitdehaag BMJ, Lissenberg-Witte BI; VWM Research Group, van der Knaap MS
Ann Neurol 2018 Aug;84(2):274-288. Epub 2018 Sep 6 doi: 10.1002/ana.25287. PMID: 30014503Free PMC Article

Recent systematic reviews

Role of inflammatory markers in the diagnosis of vascular contributions to cognitive impairment and dementia: a systematic review and meta-analysis.
Custodero C, Ciavarella A, Panza F, Gnocchi D, Lenato GM, Lee J, Mazzocca A, Sabbà C, Solfrizzi V
Geroscience 2022 Jun;44(3):1373-1392. Epub 2022 Apr 29 doi: 10.1007/s11357-022-00556-w. PMID: 35486344Free PMC Article
Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.
Mühlbauer V, Möhler R, Dichter MN, Zuidema SU, Köpke S, Luijendijk HJ
Cochrane Database Syst Rev 2021 Dec 17;12(12):CD013304. doi: 10.1002/14651858.CD013304.pub2. PMID: 34918337Free PMC Article
Cannabinoids for the treatment of dementia.
Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L
Cochrane Database Syst Rev 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2. PMID: 34532852Free PMC Article
The Prevalence of Dementia: A Systematic Review and Meta-Analysis.
Cao Q, Tan CC, Xu W, Hu H, Cao XP, Dong Q, Tan L, Yu JT
J Alzheimers Dis 2020;73(3):1157-1166. doi: 10.3233/JAD-191092. PMID: 31884487
The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.
Debette S, Markus HS
BMJ 2010 Jul 26;341:c3666. doi: 10.1136/bmj.c3666. PMID: 20660506Free PMC Article

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