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Leukoencephalopathy with vanishing white matter 2(VWM2)

MedGen UID:
1841040
Concept ID:
C5830404
Disease or Syndrome
Synonyms: Leukoencephalopathy with vanishing white matter 2, with or without ovarian failure; VWM2
 
Gene (location): EIF2B2 (14q24.3)
 
Monarch Initiative: MONDO:0957870
OMIM®: 620312

Definition

Leukoencephalopathy with vanishing white matter-2 (VWM2) is a chronic and progressive autosomal recessive leukoencephalopathy characterized by neurologic deterioration with cerebellar ataxia, spasticity, and relatively mild mental decline. Severity ranges from onset at birth with death in infancy to mild cases with later and even adult onset. Initial development may be normal. Episodes of rapid deterioration occur following febrile infection or minor head trauma. Death occurs after a variable period usually of a few years to a few decades, usually following an episode of fever and coma. Affected females may have ovarian failure manifest as primary or secondary amenorrhea. 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 Leegwater et al., 2001, van der Knaap et al., 2003). For a discussion of genetic heterogeneity of VWM, see 603896. [from OMIM]

Clinical features

From HPO
Premature ovarian insufficiency
MedGen UID:
9963
Concept ID:
C0025322
Disease or Syndrome
Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian inssuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea.
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.
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.
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.
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.
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.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Professional guidelines

PubMed

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
Skrobot OA, Black SE, Chen C, DeCarli C, Erkinjuntti T, Ford GA, Kalaria RN, O'Brien J, Pantoni L, Pasquier F, Roman GC, Wallin A, Sachdev P, Skoog I; VICCCS group, Ben-Shlomo Y, Passmore AP, Love S, Kehoe PG
Alzheimers Dement 2018 Mar;14(3):280-292. Epub 2017 Oct 19 doi: 10.1016/j.jalz.2017.09.007. PMID: 29055812
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

Wu C, Wang M, Wang X, Li W, Li S, Chen B, Niu S, Tai H, Pan H, Zhang Z
Brain 2023 Jun 1;146(6):2364-2376. doi: 10.1093/brain/awac426. PMID: 36380532Free PMC Article
Bruijstens AL, Lechner C, Flet-Berliac L, Deiva K, Neuteboom RF, Hemingway C, Wassmer E; E.U. paediatric MOG consortium, Baumann M, Bartels F, Finke C, Adamsbaum C, Hacohen Y, Rostasy K
Eur J Paediatr Neurol 2020 Nov;29:2-13. Epub 2020 Nov 4 doi: 10.1016/j.ejpn.2020.10.006. PMID: 33162302
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
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
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065

Diagnosis

Benzoni C, Moscatelli M, Farina L, Magri S, Ciano C, Scaioli V, Alverà S, Cammarata G, Bianchi-Marzoli S, Castellani M, Zito FM, Marotta G, Piacentini S, Villacara A, Mantegazza R, Gellera C, Durães J, Gouveia A, Matos A, do Carmo Macário M, Pareyson D, Taroni F, Di Bella D, Salsano E
J Neurol 2023 Sep;270(9):4219-4234. Epub 2023 May 12 doi: 10.1007/s00415-023-11762-7. PMID: 37171481
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Tormoehlen LM
Psychiatr Clin North Am 2013 Jun;36(2):277-92. Epub 2013 Apr 12 doi: 10.1016/j.psc.2013.02.006. PMID: 23688692
Ju YE, Schwedt TJ
Semin Neurol 2010 Apr;30(2):192-200. Epub 2010 Mar 29 doi: 10.1055/s-0030-1249229. PMID: 20352589Free PMC Article

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
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
Rost NS, Meschia JF, Gottesman R, Wruck L, Helmer K, Greenberg SM; DISCOVERY Investigators
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Bahar-Fuchs A, Clare L, Woods B
Cochrane Database Syst Rev 2013 Jun 5;2013(6):CD003260. doi: 10.1002/14651858.CD003260.pub2. PMID: 23740535Free PMC Article

Prognosis

Feng J, Huang C, Liang L, Li C, Wang X, Ma J, Guan X, Jiang B, Huang S, Qin P
J Am Med Dir Assoc 2023 Sep;24(9):1363-1373.e6. Epub 2023 Jul 29 doi: 10.1016/j.jamda.2023.06.025. PMID: 37527793
Jacob MA, Cai M, van de Donk V, Bergkamp M, Marques J, Norris DG, Kessels RPC, Claassen JAHR, Duering M, Tuladhar AM, Leeuw FE
Am J Psychiatry 2023 Jul 1;180(7):508-518. Epub 2023 Apr 19 doi: 10.1176/appi.ajp.20220380. PMID: 37073486
Macchi ZA, Carlisle TC, Filley CM
J Neurol Sci 2022 Nov 15;442:120420. Epub 2022 Sep 13 doi: 10.1016/j.jns.2022.120420. PMID: 36156344Free PMC Article
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Tormoehlen LM
Psychiatr Clin North Am 2013 Jun;36(2):277-92. Epub 2013 Apr 12 doi: 10.1016/j.psc.2013.02.006. PMID: 23688692

Clinical prediction guides

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
Benzoni C, Moscatelli M, Farina L, Magri S, Ciano C, Scaioli V, Alverà S, Cammarata G, Bianchi-Marzoli S, Castellani M, Zito FM, Marotta G, Piacentini S, Villacara A, Mantegazza R, Gellera C, Durães J, Gouveia A, Matos A, do Carmo Macário M, Pareyson D, Taroni F, Di Bella D, Salsano E
J Neurol 2023 Sep;270(9):4219-4234. Epub 2023 May 12 doi: 10.1007/s00415-023-11762-7. PMID: 37171481
Yang W, Jung KH, Kang DW, Lee EJ, Jeong HY, Chung M, Kim Y, Ha J, Kim JM, Lee SH
Neurology 2023 May 2;100(18):e1912-e1921. Epub 2023 Mar 6 doi: 10.1212/WNL.0000000000207130. PMID: 36878709Free 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
Berger JR, Major EO
Semin Neurol 1999;19(2):193-200. doi: 10.1055/s-2008-1040837. PMID: 10718540

Recent systematic reviews

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
Guay-Gagnon M, Vat S, Forget MF, Tremblay-Gravel M, Ducharme S, Nguyen QD, Desmarais P
J Sleep Res 2022 Oct;31(5):e13589. Epub 2022 Apr 2 doi: 10.1111/jsr.13589. PMID: 35366021
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
Debette S, Markus HS
BMJ 2010 Jul 26;341:c3666. doi: 10.1136/bmj.c3666. PMID: 20660506Free PMC Article

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