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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.
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
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.
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.
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.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
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.

Professional guidelines

PubMed

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
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
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

Recent clinical studies

Etiology

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
Marelli C, Salsano E, Politi LS, Labauge P
J Neurol Neurosurg Psychiatry 2019 Feb;90(2):211-218. Epub 2018 Aug 27 doi: 10.1136/jnnp-2018-318666. PMID: 30150321
Dichgans M, Leys D
Circ Res 2017 Feb 3;120(3):573-591. doi: 10.1161/CIRCRESAHA.116.308426. PMID: 28154105
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
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

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
Marelli C, Salsano E, Politi LS, Labauge P
J Neurol Neurosurg Psychiatry 2019 Feb;90(2):211-218. Epub 2018 Aug 27 doi: 10.1136/jnnp-2018-318666. PMID: 30150321
Tavasoli A, Armangue T, Ho CY, Whitehead M, Bornhorst M, Rhee J, Hwang EI, Wells EM, Packer R, van der Knaap MS, Bugiani M, Vanderver A
J Child Neurol 2017 Feb;32(2):184-187. Epub 2016 Oct 10 doi: 10.1177/0883073816673263. PMID: 28112050
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
Tormoehlen LM
Neurol Clin 2011 Aug;29(3):591-605. doi: 10.1016/j.ncl.2011.05.005. PMID: 21803212

Therapy

Fumagalli F, Calbi V, Natali Sora MG, Sessa M, Baldoli C, Rancoita PMV, Ciotti F, Sarzana M, Fraschini M, Zambon AA, Acquati S, Redaelli D, Attanasio V, Miglietta S, De Mattia F, Barzaghi F, Ferrua F, Migliavacca M, Tucci F, Gallo V, Del Carro U, Canale S, Spiga I, Lorioli L, Recupero S, Fratini ES, Morena F, Silvani P, Calvi MR, Facchini M, Locatelli S, Corti A, Zancan S, Antonioli G, Farinelli G, Gabaldo M, Garcia-Segovia J, Schwab LC, Downey GF, Filippi M, Cicalese MP, Martino S, Di Serio C, Ciceri F, Bernardo ME, Naldini L, Biffi A, Aiuti A
Lancet 2022 Jan 22;399(10322):372-383. doi: 10.1016/S0140-6736(21)02017-1. PMID: 35065785Free PMC Article
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
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
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
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

Prognosis

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
Vanderver A
Continuum (Minneap Minn) 2016 Jun;22(3):916-42. doi: 10.1212/CON.0000000000000338. PMID: 27261689Free PMC Article
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
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
Chui HC
Neurol Clin 2007 Aug;25(3):717-40, vi. doi: 10.1016/j.ncl.2007.04.003. PMID: 17659187Free PMC Article

Clinical prediction guides

Trinidad M, Hong X, Froelich S, Daiker J, Sacco J, Nguyen HP, Campagna M, Suhr D, Suhr T, LeBowitz JH, Gelb MH, Clark WT
Genome Biol 2023 Jul 21;24(1):172. doi: 10.1186/s13059-023-03001-z. PMID: 37480112Free PMC Article
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
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
Orsini JJ, Kay DM, Saavedra-Matiz CA, Wenger DA, Duffner PK, Erbe RW, Biski C, Martin M, Krein LM, Nichols M, Kurtzberg J, Escolar ML, Adams DJ, Arnold GL, Iglesias A, Galvin-Parton P, Kronn DF, Kwon JM, Levy PA, Pellegrino JE, Shur N, Wasserstein MP, Caggana M; New York State Krabbe Disease Consortium
Genet Med 2016 Mar;18(3):239-48. Epub 2016 Jan 21 doi: 10.1038/gim.2015.211. PMID: 26795590
Mortamais M, Artero S, Ritchie K
Int Rev Psychiatry 2013 Dec;25(6):686-98. doi: 10.3109/09540261.2013.838151. PMID: 24423222Free PMC Article

Recent systematic reviews

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
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
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
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
Debette S, Markus HS
BMJ 2010 Jul 26;341:c3666. doi: 10.1136/bmj.c3666. PMID: 20660506Free PMC Article

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