[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

Warning: The NCBI web site requires JavaScript to function. more...

U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Leukoencephalopathy with vanishing white matter 4(VWM4)

MedGen UID:
1841042
Concept ID:
C5830406
Disease or Syndrome
Synonyms: Leukoencephalopathy with vanishing white matter 4, with or without ovarian failure; VWM4
 
Gene (location): EIF2B4 (2p23.3)
 
Monarch Initiative: MONDO:0957872
OMIM®: 620314

Definition

Leukoencephalopathy with vanishing white matter-4 (VWM4) is a chronic and progressive autosomal recessive leukoencephalopathy characterized by neurologic deterioration with cerebellar ataxia, spasticity, and relatively mild mental decline. Onset is usually in childhood; early development may be normal. Female patients may experience ovarian failure. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy are diagnostic and show a diffuse abnormality of the cerebral white matter beginning in the presymptomatic stage, with increasing amounts of the abnormal white matter vanishing and being replaced by cerebrospinal fluid; autopsy confirms these findings (summary by van der Knaap et al., 2002 and Fogli et al., 2003). For a discussion of genetic heterogeneity of VWM, see 603896. [from OMIM]

Clinical features

From HPO
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
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.
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.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
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.
Corpus callosum atrophy
MedGen UID:
96560
Concept ID:
C0431370
Finding
The presence of atrophy (wasting) of the corpus callosum.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Professional guidelines

PubMed

Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, van Trotsenburg ASP, Mochel F, Sevin C, Regelmann MO, Tritos NA, Halper A, Lachmann RH, Davison J, Raymond GV, Lund TC, Orchard PJ, Kuehl JS, Lindemans CA, Caruso P, Turk BR, Moser AB, Vaz FM, Ferdinandusse S, Kemp S, Fatemi A, Eichler FS, Huffnagel IC
Neurology 2022 Nov 22;99(21):940-951. Epub 2022 Sep 29 doi: 10.1212/WNL.0000000000201374. PMID: 36175155Free PMC Article
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
Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O'Neill LA
Nat Med 2015 Mar;21(3):248-55. Epub 2015 Feb 16 doi: 10.1038/nm.3806. PMID: 25686105Free PMC Article

Recent clinical studies

Etiology

Rajeev V, Fann DY, Dinh QN, Kim HA, De Silva TM, Lai MKP, Chen CL, Drummond GR, Sobey CG, Arumugam TV
Theranostics 2022;12(4):1639-1658. Epub 2022 Jan 16 doi: 10.7150/thno.68304. PMID: 35198062Free 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
Barañano KW
Semin Neurol 2016 Aug;36(4):362-6. Epub 2016 Sep 19 doi: 10.1055/s-0036-1585455. PMID: 27643905
Kalaria RN, Akinyemi R, Ihara M
Biochim Biophys Acta 2016 May;1862(5):915-25. Epub 2016 Jan 22 doi: 10.1016/j.bbadis.2016.01.015. PMID: 26806700Free PMC Article
Tan CS, Koralnik IJ
Lancet Neurol 2010 Apr;9(4):425-37. doi: 10.1016/S1474-4422(10)70040-5. PMID: 20298966Free PMC Article

Diagnosis

Abdel-Mannan O, Hacohen Y
Handb Clin Neurol 2024;204:369-398. doi: 10.1016/B978-0-323-99209-1.00001-6. PMID: 39322390
Marignier R, Hacohen Y, Cobo-Calvo A, Pröbstel AK, Aktas O, Alexopoulos H, Amato MP, Asgari N, Banwell B, Bennett J, Brilot F, Capobianco M, Chitnis T, Ciccarelli O, Deiva K, De Sèze J, Fujihara K, Jacob A, Kim HJ, Kleiter I, Lassmann H, Leite MI, Linington C, Meinl E, Palace J, Paul F, Petzold A, Pittock S, Reindl M, Sato DK, Selmaj K, Siva A, Stankoff B, Tintore M, Traboulsee A, Waters P, Waubant E, Weinshenker B, Derfuss T, Vukusic S, Hemmer B
Lancet Neurol 2021 Sep;20(9):762-772. doi: 10.1016/S1474-4422(21)00218-0. PMID: 34418402
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
Tan CS, Koralnik IJ
Lancet Neurol 2010 Apr;9(4):425-37. doi: 10.1016/S1474-4422(10)70040-5. PMID: 20298966Free PMC Article

Therapy

Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, van Trotsenburg ASP, Mochel F, Sevin C, Regelmann MO, Tritos NA, Halper A, Lachmann RH, Davison J, Raymond GV, Lund TC, Orchard PJ, Kuehl JS, Lindemans CA, Caruso P, Turk BR, Moser AB, Vaz FM, Ferdinandusse S, Kemp S, Fatemi A, Eichler FS, Huffnagel IC
Neurology 2022 Nov 22;99(21):940-951. Epub 2022 Sep 29 doi: 10.1212/WNL.0000000000201374. PMID: 36175155Free PMC Article
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
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
Zhu J, Eichler F, Biffi A, Duncan CN, Williams DA, Majzoub JA
Endocr Rev 2020 Aug 1;41(4):577-93. doi: 10.1210/endrev/bnaa013. PMID: 32364223Free 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

Abdel-Mannan O, Hacohen Y
Handb Clin Neurol 2024;204:369-398. doi: 10.1016/B978-0-323-99209-1.00001-6. PMID: 39322390
Rindi LV, Zaçe D, Braccialarghe N, Massa B, Barchi V, Iannazzo R, Fato I, De Maria F, Kontogiannis D, Malagnino V, Sarmati L, Iannetta M
Drug Saf 2024 Apr;47(4):333-354. Epub 2024 Feb 7 doi: 10.1007/s40264-023-01383-4. PMID: 38321317
Zhang LJ, Tian DC, Yang L, Shi K, Liu Y, Wang Y, Shi FD
Stroke Vasc Neurol 2024 Aug 27;9(4):344-350. doi: 10.1136/svn-2023-002791. PMID: 37699727Free PMC Article
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
Jimbo D, Kimura Y, Taniguchi M, Inoue M, Urakami K
Psychogeriatrics 2009 Dec;9(4):173-9. doi: 10.1111/j.1479-8301.2009.00299.x. PMID: 20377818

Clinical prediction guides

Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, van Trotsenburg ASP, Mochel F, Sevin C, Regelmann MO, Tritos NA, Halper A, Lachmann RH, Davison J, Raymond GV, Lund TC, Orchard PJ, Kuehl JS, Lindemans CA, Caruso P, Turk BR, Moser AB, Vaz FM, Ferdinandusse S, Kemp S, Fatemi A, Eichler FS, Huffnagel IC
Neurology 2022 Nov 22;99(21):940-951. Epub 2022 Sep 29 doi: 10.1212/WNL.0000000000201374. PMID: 36175155Free PMC Article
van de Stadt SIW, Huffnagel IC, Turk BR, van der Knaap MS, Engelen M
Neuropediatrics 2021 Aug;52(4):252-260. Epub 2021 Jun 30 doi: 10.1055/s-0041-1730937. PMID: 34192790
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
Jimbo D, Kimura Y, Taniguchi M, Inoue M, Urakami K
Psychogeriatrics 2009 Dec;9(4):173-9. doi: 10.1111/j.1479-8301.2009.00299.x. PMID: 20377818

Recent systematic reviews

Rindi LV, Zaçe D, Braccialarghe N, Massa B, Barchi V, Iannazzo R, Fato I, De Maria F, Kontogiannis D, Malagnino V, Sarmati L, Iannetta M
Drug Saf 2024 Apr;47(4):333-354. Epub 2024 Feb 7 doi: 10.1007/s40264-023-01383-4. PMID: 38321317
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
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, 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
Debette S, Markus HS
BMJ 2010 Jul 26;341:c3666. doi: 10.1136/bmj.c3666. PMID: 20660506Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...