MCID: MGL002
MIFTS: 50

Megalencephalic Leukoencephalopathy with Subcortical Cysts malady

Genetic diseases, Rare diseases, Neuronal diseases categories

Aliases & Classifications for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Sources:
45OMIM, 10diseasecard, 19GeneReviews, 41NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 47Orphanet, 22GTR, 60UMLS, 26ICD10 via Orphanet, 61UMLS via Orphanet
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Megalencephalic Leukoencephalopathy with Subcortical Cysts, Aliases & Descriptions:

Name: Megalencephalic Leukoencephalopathy with Subcortical Cysts 45 10 19 41 20 21 47 60
Vacuolating Megalencephalic Leukoencephalopathy with Subcortical Cysts 19 41 21 47
Mlc 41 21 47
Megalencephalic Leukoencephalopathy with Subcortical Cysts 1 20 22
Leukoencephalopathy with Swelling and Cysts 41 21
Megalencephaly - Cystic Leukodystrophy 41 47
Megalencephalic Leukodystrophy 41 47
Van Der Knaap Syndrome 41 47
 
Lvm 41 21
Leukoencephalopathy with Swelling and a Discrepantly Mild Course 21
Infantile Leukoencephalopathy and Megalencephaly 21
Megalencephaly-Cystic Leukodystrophy 41
Vacuolating Leukoencephalopathy 21
Van Der Knapp Disease 21
Van Der Knaap Disease 19
Vl 21


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

47
megalencephalic leukoencephalopathy with subcortical cysts:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal


External Ids:

OMIM45 604004
Orphanet47 2478
ICD10 via Orphanet26 E75.2
UMLS via Orphanet61 C1858854

Summaries for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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NIH Rare Diseases:41 Megalencephalic leukoencephalopathy with subcortical cysts is a condition that affects brain development and function. children with this condition have an enlarged brain (megalencephaly) that is evident at birth or within the first year of life. they also have an abnormality of the brain's white matter (leukoencephalopathy). the leukoencephalopathy may ultimately result in abnormal muscle tensing (spasticity), difficulty coordinating movements (ataxia), cysts in the brain (subcortical cysts), abnormal muscle tone (dystonia), swallowing difficulties, speech difficulties, and seizures. despite the brain abnormalities people with this condition tend to have only mild to moderate learning impairment. this condition may affect a child’s ability to walk, however some children are able to walk well into adulthood. it is important to protect people with mlc from even mild head trauma, because head trauma can cause further impairments and may lead to coma. this condition is genetic and is passed through families in an autosomal recessive pattern. it is most often caused by changes in the mlc1 gene. last updated: 6/4/2009

MalaCards based summary: Megalencephalic Leukoencephalopathy with Subcortical Cysts, also known as vacuolating megalencephalic leukoencephalopathy with subcortical cysts, is related to megalencephalic leukoencephalopathy with subcortical cysts 2a and megalencephalic leukoencephalopathy with subcortical cysts 2b, remitting, with or without mental retardation, and has symptoms including autosomal recessive inheritance, macrocephaly and seizures. An important gene associated with Megalencephalic Leukoencephalopathy with Subcortical Cysts is MLC1 (megalencephalic leukoencephalopathy with subcortical cysts 1), and among its related pathways are Hepatic ABC Transporters and Mineral absorption. The compounds chlorambucil and sodium have been mentioned in the context of this disorder. Affiliated tissues include brain, cortex and monocytes, and related mouse phenotypes are hearing/vestibular/ear and cardiovascular system.

Genetics Home Reference:21 Megalencephalic leukoencephalopathy with subcortical cysts is a progressive condition that affects brain development and function. Individuals with this condition typically have an enlarged brain (megalencephaly) that is evident at birth or within the first year of life. Megalencephaly leads to an increase in the size of the head. Affected people also have leukoencephalopathy, an abnormality of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In megalencephalic leukoencephalopathy with subcortical cysts, the myelin is swollen and contains numerous fluid-filled pockets (vacuoles). Over time, the swelling decreases and the myelin begins to waste away (atrophy). Individuals affected with this condition may develop cysts in the brain; because these cysts form below an area of the brain called the cerebral cortex, they are called subcortical cysts. These cysts can grow in size and number.

OMIM:45 Megalencephalic leukoencephalopathy with subcortical cysts is a leukodystrophy characterized by early-onset... (604004) more...

Wikipedia:63 Megalencephalic leukoencephalopathy with subcortical cysts (MLC, or Van der Knaap disease) is a form of... more...

GeneReviews summary for mlc

Related Diseases for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Graphical network of the top 20 diseases related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:



Diseases related to megalencephalic leukoencephalopathy with subcortical cysts

Symptoms for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Symptoms by clinical synopsis from OMIM:

604004

Clinical features from OMIM:

604004

HPO human phenotypes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

(show all 11)
id Description Frequency HPO Source Accession
1 autosomal recessive inheritance HP:0000007
2 macrocephaly HP:0000256
3 seizures HP:0001250
4 ataxia HP:0001251
5 intellectual disability, mild HP:0001256
6 spasticity HP:0001257
7 motor delay HP:0001270
8 megalencephaly HP:0001355
9 infantile onset HP:0003593
10 diffuse spongiform leukoencephalopathy HP:0006943
11 diffuse swelling of cerebral white matter HP:0007341

Drugs & Therapeutics for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Drug clinical trials:

Search ClinicalTrials for Megalencephalic Leukoencephalopathy with Subcortical Cysts

Search NIH Clinical Center for Megalencephalic Leukoencephalopathy with Subcortical Cysts

Genetic Tests for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Genetic tests related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

id Genetic test Affiliating Genes
1 Megalencephalic Leukoencephalopathy with Subcortical Cysts20 MLC1
2 Megalencephalic Leukoencephalopathy with Subcortical Cysts 120 22

Anatomical Context for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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MalaCards organs/tissues related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

31
Brain, Cortex, Monocytes

Animal Models for Megalencephalic Leukoencephalopathy with Subcortical Cysts or affiliated genes

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MGI Mouse Phenotypes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053778.7FBLN1, AQP4, TRPV4
2MP:00053858.2TRPV4, AQP4, CLCN2, FBLN1, ATP1B1
3MP:00107718.1TRPV4, BAMBI, MCL1, FBLN1

Publications for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Articles related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

(show top 50)    (show all 59)
idTitleAuthorsYear
1
Eight novel mutations in MLC1 from 18 Iranian patients with megalencephalic leukoencephalopathy with subcortical cysts. (25497041)
2015
2
Molecular prenatal diagnosis of megalencephalic leukoencephalopathy with subcortical cysts in a child from southwest of Iran. (25767710)
2015
3
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) - a case with clinical and magnetic resonance imaging (MRI) dissociation. (25742591)
2015
4
Megalencephalic leukoencephalopathy with subcortical cysts caused by compound heterozygous mutations in MLC1, in patients with and without subcortical cysts in the brain. (25796299)
2015
5
Teaching neuroimages: Resolution of MRI abnormalities in megalencephalic leukoencephalopathy with subcortical cysts. (24821940)
2014
6
Twelve-year monitoring of a patient with megalencephalic leukoencephalopathy with subcortical cysts. (24584635)
2014
7
Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans. (24824219)
2014
8
Megalencephalic leukoencephalopathy with subcortical cysts protein-1 modulates endosomal pH and protein trafficking in astrocytes: relevance to MLC disease pathogenesis. (24561067)
2014
9
Clinical, Neuroimaging, and Genetic Characteristics of Megalencephalic Leukoencephalopathy With Subcortical Cysts inA Egyptian Patients. (24315536)
2014
10
Expanding the spectrum of megalencephalic leukoencephalopathy with subcortical cysts in two patients with GLIALCAM mutations. (24202401)
2013
11
Megalencephalic leukoencephalopathy with subcortical cysts. (24273671)
2013
12
Monocytes and macrophages as biomarkers for the diagnosis of megalencephalic leukoencephalopathy with subcortical cysts. (23851226)
2013
13
An unusually mild presentation of megalencephalic leukoencephalopathy with subcortical cysts. (23485252)
2013
14
Megalencephalic leukoencephalopathy with subcortical cysts in all three siblings of a non-Aggarwal Indian family. (22919198)
2012
15
Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. (22328087)
2012
16
Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis. (23079554)
2012
17
Functional studies of MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts. (22416245)
2012
18
A Japanese adult case of megalencephalic leukoencephalopathy with subcortical cysts with a good long-term prognosis. (22382567)
2012
19
Megalencephalic leukoencephalopathy with subcortical cysts: A report of four cases. (21977097)
2011
20
Molecular mechanisms of MLC1 and GLIALCAM mutations in megalencephalic leukoencephalopathy with subcortical cysts. (21624973)
2011
21
Identification of novel MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts (MLC). (21160490)
2011
22
Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism. (21419380)
2011
23
A commentary on Identification of novel MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts (MLC). (21307857)
2011
24
Two cases with megalencephalic leukoencephalopathy with subcortical cysts and MLC1 mutations in the Turkish population. (20560255)
2010
25
Analysis of CLCN2 as candidate gene for megalencephalic leukoencephalopathy with subcortical cysts. (20187760)
2010
26
Megalencephalic leukoencephalopathy with subcortical cysts: a third confirmed case with literature review. (18821826)
2009
27
Megalencephalic leukoencephalopathy with subcortical cysts in a Tunisian boy. (19168821)
2009
28
Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects. (18757878)
2008
29
Megalencephalic leukoencephalopathy with subcortical cysts: report of 4 new cases]. (18772751)
2008
30
Dysmyelinating neuropathy in benign form of megalencephalic leukoencephalopathy with subcortical cysts: a novel observation from south India. (18040118)
2007
31
SPECT revealed cortical dysfunction in a patient who had genetically definite megalencephalic leukoencephalopathy with subcortical cysts. (17507156)
2007
32
Late-onset neuropsychological symptoms in a Japanese patient with megalencephalic leukoencephalopathy with subcortical cysts. (17236107)
2006
33
Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1. (16470554)
2006
34
An adult case of megalencephalic leukoencephalopathy with subcortical cysts with S93L mutation in MLC1 gene: a case report and diffusion MRI. (17077634)
2006
35
Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1. (16652334)
2006
36
Megalencephalic leukoencephalopathy with subcortical cysts. (15695862)
2005
37
Megalencephalic leukoencephalopathy with subcortical cysts. (15758546)
2005
38
Megalencephalic leukoencephalopathy with subcortical cysts in two siblings owing to two novel mutations: case reports and review of the literature. (15832614)
2005
39
Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts. (15367490)
2004
40
Megalencephalic leukoencephalopathy with subcortical cysts. (15163886)
2004
41
A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): molecular genetic study. (12850517)
2003
42
Megalencephalic leukoencephalopathy with subcortical cysts: MRI and proton spectroscopic features. (14742938)
2003
43
Megalencephalic leukoencephalopathy with subcortical cysts. (14572144)
2003
44
Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI. (12684714)
2003
45
Clinical and genetic heterogeneity in megalencephalic leukoencephalopathy with subcortical cysts (MLC). (12973664)
2003
46
Epilepsy in vacuolating megalencephalic leukoencephalopathy with subcortical cysts. (12915085)
2003
47
The brain-specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain. (14603469)
2003
48
Consciousness disturbances in megalencephalic leukoencephalopathy with subcortical cysts. (12973663)
2003
49
Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts. (11935341)
2002
50
Megalencephalic Leukoencephalopathy with Subcortical Cysts (20301707)
1993

Variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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UniProtKB/Swiss-Prot genetic disease variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts:

62 (show all 15)
id Symbol AA change Variation ID SNP ID
1MLC1p.Ser93LeuVAR_011699rs80358245
2MLC1p.Thr118ArgVAR_011700rs281875316
3MLC1p.Gly212ArgVAR_011701rs281875317
4MLC1p.Ser280LeuVAR_011702rs121908341
5MLC1p.Gly59GluVAR_017438rs80358242
6MLC1p.Pro92SerVAR_017439rs121908345
7MLC1p.Asn141LysVAR_017440rs121908343
8MLC1p.Asn141SerVAR_017441rs121908344
9MLC1p.Ser69LeuVAR_067762rs281875309
10MLC1p.Met80IleVAR_067763rs281875310
11MLC1p.Arg84CysVAR_067764rs281875311
12MLC1p.Cys125ArgVAR_067765rs281875314
13MLC1p.Ala245ProVAR_067766rs281875312
14MLC1p.Ser246ArgVAR_067767rs281875315
15MLC1p.Thr320LysVAR_067768rs281875313

Clinvar genetic disease variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts:

6 (show all 21)
id Gene Variation Type Significance SNP ID Assembly Location
1MLC1NM_015166.3(MLC1): c.178-10T> Asingle nucleotide variantPathogenicrs80358243GRCh37Chr 22, 50521612: 50521612
2MLC1NM_015166.3: c.298_423+108deldeletionPathogenicGRCh37Chr 22, 50518239: 50518796
3HEPACAMNM_152722.4(HEPACAM): c.587C> A (p.Ser196Tyr)single nucleotide variantPathogenicrs387907049GRCh37Chr 11, 124793747: 124793747
4HEPACAMHEPACAM, TRP263TERundetermined variantPathogenic
5HEPACAMNM_152722.4(HEPACAM): c.275G> A (p.Arg92Gln)single nucleotide variantPathogenicrs387907050GRCh37Chr 11, 124794776: 124794776
6HEPACAMNM_152722.4(HEPACAM): c.631G> A (p.Asp211Asn)single nucleotide variantPathogenicrs387907051GRCh37Chr 11, 124793703: 124793703
7HEPACAMNM_152722.4(HEPACAM): c.292C> T (p.Arg98Cys)single nucleotide variantPathogenicrs387907052GRCh37Chr 11, 124794759: 124794759
8HEPACAMNM_152722.4(HEPACAM): c.265G> A (p.Gly89Ser)single nucleotide variantPathogenicrs387907053GRCh37Chr 11, 124794786: 124794786
9HEPACAMNM_152722.4(HEPACAM): c.274C> T (p.Arg92Trp)single nucleotide variantPathogenicrs387907055GRCh37Chr 11, 124794777: 124794777
10MLC1NM_015166.3(MLC1): c.206C> T (p.Ser69Leu)single nucleotide variantPathogenicrs281875309GRCh37Chr 22, 50521574: 50521574
11MLC1NM_015166.3(MLC1): c.839C> T (p.Ser280Leu)single nucleotide variantPathogenicrs121908341GRCh37Chr 22, 50506917: 50506917
12MLC1NM_015166.3(MLC1): c.278C> T (p.Ser93Leu)single nucleotide variantPathogenicrs80358245GRCh37Chr 22, 50518816: 50518816
13MLC1MLC1, 7-BP DEL, NT564deletionPathogenic
14MLC1MLC1, IVS10AS, A-G, -2single nucleotide variantPathogenic
15MLC1NM_015166.3(MLC1): c.423C> A (p.Asn141Lys)single nucleotide variantPathogenicrs121908343GRCh37Chr 22, 50518347: 50518347
16MLC1NM_015166.3(MLC1): c.422A> G (p.Asn141Ser)single nucleotide variantPathogenicrs121908344GRCh37Chr 22, 50518348: 50518348
17MLC1NM_015166.3(MLC1): c.274C> T (p.Pro92Ser)single nucleotide variantPathogenicrs121908345GRCh37Chr 22, 50518820: 50518820
18MLC1NM_015166.3(MLC1): c.594_597delCTCA (p.Tyr198Terfs)deletionPathogenicrs267607236GRCh37Chr 22, 50515270: 50515273
19MLC1NM_015166.3(MLC1): c.176G> A (p.Gly59Glu)single nucleotide variantPathogenicrs80358242GRCh37Chr 22, 50523156: 50523156
20MLC1NM_015166.3(MLC1): c.135dupC (p.Cys46Leufs)duplicationPathogenicrs80358241GRCh37Chr 22, 50523196: 50523197
21MLC1MLC1, 17-BP DEL, G INSindelPathogenic

Expression for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Search GEO for disease gene expression data for Megalencephalic Leukoencephalopathy with Subcortical Cysts.

Pathways for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Pathways related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.7CLCN2, ATP1B1
29.7CLCN2, ATP1B1
39.7AQP4, ATP1B1
4
Show member pathways
9.3ATP1B1, CLCN2, TRPV4
5
Show member pathways
8.9TRPV4, AQP4, CLCN2, ATP1B1

Compounds for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Sources:
43Novoseek, 12DrugBank, 24HMDB
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Compounds related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards Suite gene sharing:

idCompoundScoreTop Affiliating Genes
1chlorambucil43 1210.4MCL1, MGST1
2sodium43 249.6TRPV4, AQP4, CLCN2, ATP1B1

GO Terms for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Cellular components related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1cytoplasmic vesicleGO:00314109.7TRPV4, MLC1
2cell-cell junctionGO:00059119.6HEPACAM, AQP4, MLC1
3caveolaGO:00059019.5ATP1B1, MLC1
4basolateral plasma membraneGO:00163239.5AQP4, ATP1B1, MLC1
5plasma membraneGO:00058867.8MLC1, ATP1B1, CLCN2, AQP4, BAMBI, TRPV4
6integral component of membraneGO:00160217.4MGST1, MLC1, MCL1, HEPACAM, BAMBI, TRPV4

Biological processes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1regulation of response to osmotic stressGO:00474849.8MLC1, TRPV4
2hyperosmotic salinity responseGO:00425389.5AQP4, TRPV4
3ion transmembrane transportGO:00342209.3ATP1B1, CLCN2, TRPV4
4transportGO:00068109.0AQP4, CLCN2, ATP1B1, MLC1
5transmembrane transportGO:00550858.6TRPV4, AQP4, CLCN2, ATP1B1

Products for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Sources for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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3CDC
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23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
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