LCWM
MCID: LKN008
MIFTS: 35

Leukoencephalopathy, Cystic, Without Megalencephaly (LCWM)

Categories: Ear diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leukoencephalopathy, Cystic, Without Megalencephaly

MalaCards integrated aliases for Leukoencephalopathy, Cystic, Without Megalencephaly:

Name: Leukoencephalopathy, Cystic, Without Megalencephaly 57 20 72 29 13 6 39
Cystic Leukoencephalopathy Without Megalencephaly 20 43 58 36
Leukoencephalopathy with Bilateral Anterior Temporal Lobe Cysts 43 58
Rnase T2-Deficient Leukoencephalopathy 20 43
Clwm 20 58
Rnaset2-Deficient Cystic Leukoencephalopathy 43
Lbatc 43
Lcwm 72

Characteristics:

Orphanet epidemiological data:

58
leukoencephalopathy with bilateral anterior temporal lobe cysts
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
cystic leukoencephalopathy without megalencephaly
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in first year of life
phenotype is indistinguishable from congenital cytomegalovirus (cmv) infection
stable or slowly progressive course


HPO:

31
leukoencephalopathy, cystic, without megalencephaly:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Leukoencephalopathy, Cystic, Without Megalencephaly

MedlinePlus Genetics : 43 RNAse T2-deficient leukoencephalopathy is a disorder that affects the brain. People with RNAse T2-deficient leukoencephalopathy have neurological problems that become apparent during infancy; the problems generally do not worsen over time (progress). Most affected individuals have severe intellectual disability; muscle stiffness (spasticity); and a delay in developing motor skills such as sitting, crawling, and walking. Some do not learn to walk, and most do not develop the ability to speak. Other neurological features that can occur in RNAse T2-deficient leukoencephalopathy include hearing loss caused by abnormalities in the inner ear (sensorineural deafness), seizures, involuntary writhing movements of the hands (athetosis), uncontrolled muscle tensing (dystonia), and involuntary eye movements (nystagmus). In addition to the neurological problems associated with this disorder, some affected individuals have unusual facial features sometimes described as a "doll-like face."The neurological problems in this disorder are caused by abnormalities in the brain. People with this condition have leukoencephalopathy, an abnormality of the brain's white matter that can be detected with medical imaging. 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 people with RNAse T2-deficient leukoencephalopathy, myelin is not made in sufficient amounts during development, leading to patchy white matter abnormalities (lesions) in the brain. In addition, individuals with RNAse T2-deficient leukoencephalopathy may have cysts in regions of the brain called the temporal lobes and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. The white matter lesions are primarily concentrated around the cysts and the ventricles. An abnormally small head and brain size (microcephaly) often occurs in this disorder.

MalaCards based summary : Leukoencephalopathy, Cystic, Without Megalencephaly, also known as cystic leukoencephalopathy without megalencephaly, is related to macrocephaly/megalencephaly syndrome, autosomal recessive and megalencephaly. An important gene associated with Leukoencephalopathy, Cystic, Without Megalencephaly is RNASET2 (Ribonuclease T2). Affiliated tissues include brain, temporal lobe and eye, and related phenotypes are intellectual disability and global developmental delay

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 85136 Definition Cystic leukoencephalopathy without megalencephaly is characterised by non-progressive leukoencephalopathy, bilateral cysts in the anterior part of the temporal lobe, cerebral white matter anomalies and severe psychomotor impairment. Less than 50 patients have been described in the literature so far. Inheritance is most likely autosomal recessive.

KEGG : 36 Cystic leukoencephalopathy without megalencephaly is an autosomal recessive infantile-onset neurological disorder. The affected individuals are asymptomatic at birth and show a static encephalopathy with normo- or microcephaly and psychomotor impairment within the first year of life. Brain magnetic resonance imaging (MRI) shows bilateral anterior temporal lobe cystic lesions and enlarged inferior horns combined with multifocal white matter alterations. Loss-of-function mutations in the gene encoding the RNASET2 glycoprotein lead to this disorder.

UniProtKB/Swiss-Prot : 72 Leukoencephalopathy, cystic, without megalencephaly: An infantile-onset syndrome of cerebral leukoencephalopathy. Affected newborns develop microcephaly and neurologic abnormalities including psychomotor impairment, seizures and sensorineural hearing impairment. The brain shows multifocal white matter lesions, anterior temporal lobe subcortical cysts, pericystic abnormal myelination, ventriculomegaly and intracranial calcifications.

More information from OMIM: 612951

Related Diseases for Leukoencephalopathy, Cystic, Without Megalencephaly

Diseases related to Leukoencephalopathy, Cystic, Without Megalencephaly via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 macrocephaly/megalencephaly syndrome, autosomal recessive 10.4
2 megalencephaly 10.4
3 spasticity 10.4
4 branchiootic syndrome 1 10.3
5 alcohol-related neurodevelopmental disorder 10.2
6 autosomal recessive disease 10.2
7 lysosomal disease 10.2
8 human cytomegalovirus infection 10.1
9 leukodystrophy 10.1
10 microcephaly 10.1
11 inherited metabolic disorder 10.1
12 congenital cytomegalovirus 10.1

Graphical network of the top 20 diseases related to Leukoencephalopathy, Cystic, Without Megalencephaly:



Diseases related to Leukoencephalopathy, Cystic, Without Megalencephaly

Symptoms & Phenotypes for Leukoencephalopathy, Cystic, Without Megalencephaly

Human phenotypes related to Leukoencephalopathy, Cystic, Without Megalencephaly:

58 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
3 motor delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001270
4 leukoencephalopathy 58 31 occasional (7.5%) Very frequent (99-80%) HP:0002352
5 lower limb spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002061
6 intracranial cystic lesion 58 31 hallmark (90%) Very frequent (99-80%) HP:0010576
7 clonus 58 31 frequent (33%) Frequent (79-30%) HP:0002169
8 microcephaly 58 31 occasional (7.5%) Frequent (79-30%) HP:0000252
9 sensorineural hearing impairment 58 31 occasional (7.5%) Frequent (79-30%) HP:0000407
10 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
11 absent speech 58 31 frequent (33%) Frequent (79-30%) HP:0001344
12 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
13 functional motor deficit 58 31 frequent (33%) Frequent (79-30%) HP:0004302
14 infantile axial hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0009062
15 spasticity 31 occasional (7.5%) HP:0001257
16 nystagmus 31 occasional (7.5%) HP:0000639
17 ataxia 31 occasional (7.5%) HP:0001251
18 cerebral calcification 31 occasional (7.5%) HP:0002514
19 delayed speech and language development 31 occasional (7.5%) HP:0000750
20 ventriculomegaly 31 occasional (7.5%) HP:0002119
21 dystonia 31 occasional (7.5%) HP:0001332
22 severe global developmental delay 31 occasional (7.5%) HP:0011344
23 athetosis 31 occasional (7.5%) HP:0002305
24 abnormal cns myelination 31 occasional (7.5%) HP:0011400
25 doll-like facies 31 occasional (7.5%) HP:0000295
26 seizure 31 occasional (7.5%) HP:0001250
27 poor speech 31 HP:0002465
28 focal white matter lesions 31 HP:0007042

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
spasticity
ataxia
ventriculomegaly
dystonia
more
Head And Neck Face:
doll-like facies

Head And Neck Head:
microcephaly (some)

Head And Neck Eyes:
nystagmus

Head And Neck Ears:
hearing loss, sensorineural

Laboratory Abnormalities:
no evidence of perinatal infection

Clinical features from OMIM®:

612951 (Updated 05-Apr-2021)

Drugs & Therapeutics for Leukoencephalopathy, Cystic, Without Megalencephaly

Search Clinical Trials , NIH Clinical Center for Leukoencephalopathy, Cystic, Without Megalencephaly

Genetic Tests for Leukoencephalopathy, Cystic, Without Megalencephaly

Genetic tests related to Leukoencephalopathy, Cystic, Without Megalencephaly:

# Genetic test Affiliating Genes
1 Leukoencephalopathy, Cystic, Without Megalencephaly 29 RNASET2

Anatomical Context for Leukoencephalopathy, Cystic, Without Megalencephaly

MalaCards organs/tissues related to Leukoencephalopathy, Cystic, Without Megalencephaly:

40
Brain, Temporal Lobe, Eye

Publications for Leukoencephalopathy, Cystic, Without Megalencephaly

Articles related to Leukoencephalopathy, Cystic, Without Megalencephaly:

# Title Authors PMID Year
1
RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection. 6 57
19525954 2009
2
Cystic leukoencephalopathy without megalencephaly: a distinct disease entity in 15 children. 61 57
15851732 2005
3
Non-progressive leukoencephalopathy with bilateral temporal cysts. 57
11589166 2001
4
A new leukoencephalopathy with bilateral anterior temporal lobe cysts. 57
9810556 1998
5
Novel RNASET2 Pathogenic Variants in an East Asian Child with Delayed Psychomotor Development. 61
29336640 2018
6
Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome. 61
27091087 2016
7
Congenital cytomegalovirus infection resembling cystic leukoencephalopathy without megalencephaly. 61
20434699 2010
8
Cystic leukoencephalopathy without megalencephaly. 61
18545798 2008

Variations for Leukoencephalopathy, Cystic, Without Megalencephaly

ClinVar genetic disease variations for Leukoencephalopathy, Cystic, Without Megalencephaly:

6 (show top 50) (show all 55)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RNASET2 NM_003730.6(RNASET2):c.550T>C (p.Cys184Arg) SNV Pathogenic 412 rs121918137 GRCh37: 6:167344549-167344549
GRCh38: 6:166931061-166931061
2 RNASET2 RNASET2, 2.5-KB DEL Deletion Pathogenic 413 GRCh37:
GRCh38:
3 RNASET2 RNASET2, IVS5AS, A-G, -2 SNV Pathogenic 414 GRCh37:
GRCh38:
4 RNASET2 RNASET2, 1-BP DEL, 332+1G Deletion Pathogenic 415 GRCh37:
GRCh38:
5 RNASET2 NM_003730.6(RNASET2):c.50_64del (p.Ala17_Leu21del) Deletion Pathogenic 416 rs1583242286 GRCh37: 6:167369607-167369621
GRCh38: 6:166956119-166956133
6 RNASET2 NM_003730.6(RNASET2):c.233C>A (p.Ser78Ter) SNV Pathogenic 872952 GRCh37:
GRCh38:
7 RNASET2 NM_003730.6(RNASET2):c.710dup (p.Leu238fs) Duplication Likely pathogenic 436545 rs763295910 GRCh37: 6:167343136-167343137
GRCh38: 6:166929648-166929649
8 RNASET2 NM_003730.6(RNASET2):c.204-14A>G SNV Uncertain significance 930667 GRCh37: 6:167360241-167360241
GRCh38: 6:166946753-166946753
9 RNASET2 NM_003730.6(RNASET2):c.131C>T (p.Pro44Leu) SNV Uncertain significance 930668 GRCh37: 6:167365992-167365992
GRCh38: 6:166952504-166952504
10 RNASET2 NM_003730.6(RNASET2):c.748C>T (p.Pro250Ser) SNV Uncertain significance 813909 rs759625896 GRCh37: 6:167343099-167343099
GRCh38: 6:166929611-166929611
11 RNASET2 NM_003730.5(RNASET2):c.-396T>C SNV Uncertain significance 356055 rs548420673 GRCh37: 6:167370066-167370066
GRCh38: 6:166956578-166956578
12 RNASET2 NM_003730.6(RNASET2):c.660G>A (p.Pro220=) SNV Uncertain significance 786739 rs74546166 GRCh37: 6:167343187-167343187
GRCh38: 6:166929699-166929699
13 RNASET2 NM_003730.5(RNASET2):c.-384G>A SNV Uncertain significance 356053 rs886061249 GRCh37: 6:167370054-167370054
GRCh38: 6:166956566-166956566
14 RNASET2 NM_003730.5(RNASET2):c.-392G>C SNV Uncertain significance 356054 rs536539036 GRCh37: 6:167370062-167370062
GRCh38: 6:166956574-166956574
15 RNASET2 NM_003730.6(RNASET2):c.567G>A (p.Gln189=) SNV Uncertain significance 417 rs1191342507 GRCh37: 6:167344532-167344532
GRCh38: 6:166931044-166931044
16 RNASET2 NM_003730.6(RNASET2):c.207C>T (p.Pro69=) SNV Uncertain significance 779708 rs184572250 GRCh37: 6:167360224-167360224
GRCh38: 6:166946736-166946736
17 RNASET2 NM_003730.6(RNASET2):c.-183del Deletion Uncertain significance 356047 rs886061248 GRCh37: 6:167369853-167369853
GRCh38: 6:166956365-166956365
18 RNASET2 NM_003730.6(RNASET2):c.-3_6del (p.Met1_Arg2del) Deletion Uncertain significance 356040 rs886061241 GRCh37: 6:167369665-167369673
GRCh38: 6:166956177-166956185
19 RNASET2 NM_003730.6(RNASET2):c.-77del Deletion Uncertain significance 356043 rs886061244 GRCh37: 6:167369747-167369747
GRCh38: 6:166956259-166956259
20 RNASET2 NM_003730.6(RNASET2):c.325C>A (p.Arg109Ser) SNV Uncertain significance 356035 rs780445402 GRCh37: 6:167356514-167356514
GRCh38: 6:166943026-166943026
21 RNASET2 NM_003730.6(RNASET2):c.-14C>A SNV Uncertain significance 356041 rs886061242 GRCh37: 6:167369684-167369684
GRCh38: 6:166956196-166956196
22 RNASET2 NM_003730.6(RNASET2):c.-104G>T SNV Uncertain significance 356044 rs886061245 GRCh37: 6:167369774-167369774
GRCh38: 6:166956286-166956286
23 RNASET2 NM_003730.6(RNASET2):c.380C>T (p.Ala127Val) SNV Uncertain significance 356033 rs117003826 GRCh37: 6:167352449-167352449
GRCh38: 6:166938961-166938961
24 RNASET2 NM_003730.6(RNASET2):c.-32A>G SNV Uncertain significance 356042 rs886061243 GRCh37: 6:167369702-167369702
GRCh38: 6:166956214-166956214
25 RNASET2 NM_003730.6(RNASET2):c.-114G>C SNV Uncertain significance 356045 rs886061246 GRCh37: 6:167369784-167369784
GRCh38: 6:166956296-166956296
26 RNASET2 NM_003730.6(RNASET2):c.652G>A (p.Glu218Lys) SNV Uncertain significance 356028 rs202105909 GRCh37: 6:167343195-167343195
GRCh38: 6:166929707-166929707
27 RNASET2 NM_003730.6(RNASET2):c.534G>A (p.Val178=) SNV Uncertain significance 356031 rs763011032 GRCh37: 6:167344565-167344565
GRCh38: 6:166931077-166931077
28 RNASET2 NM_003730.6(RNASET2):c.-203G>A SNV Uncertain significance 356048 rs567484544 GRCh37: 6:167369873-167369873
GRCh38: 6:166956385-166956385
29 RNASET2 NM_003730.6(RNASET2):c.360C>A (p.Thr120=) SNV Uncertain significance 356034 rs750265990 GRCh37: 6:167352469-167352469
GRCh38: 6:166938981-166938981
30 RNASET2 NM_003730.6(RNASET2):c.-251G>C SNV Uncertain significance 356050 rs373504059 GRCh37: 6:167369921-167369921
GRCh38: 6:166956433-166956433
31 RNASET2 NM_003730.6(RNASET2):c.224G>A (p.Cys75Tyr) SNV Uncertain significance 356036 rs886061240 GRCh37: 6:167360207-167360207
GRCh38: 6:166946719-166946719
32 RNASET2 NM_003730.6(RNASET2):c.-176C>T SNV Uncertain significance 356046 rs886061247 GRCh37: 6:167369846-167369846
GRCh38: 6:166956358-166956358
33 RNASET2 NM_003730.6(RNASET2):c.22G>A (p.Gly8Arg) SNV Uncertain significance 873505 GRCh37: 6:167369649-167369649
GRCh38: 6:166956161-166956161
34 RNASET2 NM_003730.6(RNASET2):c.568-4T>C SNV Uncertain significance 903948 GRCh37: 6:167343283-167343283
GRCh38: 6:166929795-166929795
35 RNASET2 NM_003730.6(RNASET2):c.563G>T (p.Ser188Ile) SNV Uncertain significance 903949 GRCh37: 6:167344536-167344536
GRCh38: 6:166931048-166931048
36 RNASET2 NM_003730.6(RNASET2):c.-69C>T SNV Uncertain significance 906341 GRCh37: 6:167369739-167369739
GRCh38: 6:166956251-166956251
37 RNASET2 NM_003730.6(RNASET2):c.-72C>G SNV Uncertain significance 906342 GRCh37: 6:167369742-167369742
GRCh38: 6:166956254-166956254
38 RNASET2 NM_003730.6(RNASET2):c.-155C>T SNV Uncertain significance 906343 GRCh37: 6:167369825-167369825
GRCh38: 6:166956337-166956337
39 RNASET2 NM_003730.6(RNASET2):c.648G>C (p.Pro216=) SNV Uncertain significance 907287 GRCh37: 6:167343199-167343199
GRCh38: 6:166929711-166929711
40 RNASET2 NM_003730.6(RNASET2):c.-221G>A SNV Uncertain significance 907348 GRCh37: 6:167369891-167369891
GRCh38: 6:166956403-166956403
41 RNASET2 NM_003730.6(RNASET2):c.707G>A (p.Arg236Gln) SNV Likely benign 716206 rs146590748 GRCh37: 6:167343140-167343140
GRCh38: 6:166929652-166929652
42 RNASET2 NM_003730.6(RNASET2):c.741C>A (p.Phe247Leu) SNV Likely benign 356026 rs140357917 GRCh37: 6:167343106-167343106
GRCh38: 6:166929618-166929618
43 RNASET2 NM_003730.6(RNASET2):c.696C>T (p.Ala232=) SNV Likely benign 735217 rs537280779 GRCh37: 6:167343151-167343151
GRCh38: 6:166929663-166929663
44 RNASET2 NM_003730.6(RNASET2):c.643G>A (p.Glu215Lys) SNV Likely benign 356030 rs41269593 GRCh37: 6:167343204-167343204
GRCh38: 6:166929716-166929716
45 RNASET2 NM_003730.6(RNASET2):c.426C>T (p.Tyr142=) SNV Benign 782746 rs34346305 GRCh37: 6:167352403-167352403
GRCh38: 6:166938915-166938915
46 RNASET2 NM_003730.6(RNASET2):c.214A>G (p.Ser72Gly) SNV Benign 779640 rs115956642 GRCh37: 6:167360217-167360217
GRCh38: 6:166946729-166946729
47 RNASET2 NM_003730.6(RNASET2):c.-227G>T SNV Benign 356049 rs1044059 GRCh37: 6:167369897-167369897
GRCh38: 6:166956409-166956409
48 RNASET2 NM_003730.6(RNASET2):c.16C>T (p.Leu6=) SNV Benign 356039 rs11557915 GRCh37: 6:167369655-167369655
GRCh38: 6:166956167-166956167
49 RNASET2 NM_003730.6(RNASET2):c.147+3G>A SNV Benign 356037 rs78446649 GRCh37: 6:167365973-167365973
GRCh38: 6:166952485-166952485
50 RNASET2 NM_003730.6(RNASET2):c.-321G>T SNV Benign 356051 rs182515066 GRCh37: 6:167369991-167369991
GRCh38: 6:166956503-166956503

UniProtKB/Swiss-Prot genetic disease variations for Leukoencephalopathy, Cystic, Without Megalencephaly:

72
# Symbol AA change Variation ID SNP ID
1 RNASET2 p.Cys184Arg VAR_063596 rs121918137

Expression for Leukoencephalopathy, Cystic, Without Megalencephaly

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Pathways for Leukoencephalopathy, Cystic, Without Megalencephaly

GO Terms for Leukoencephalopathy, Cystic, Without Megalencephaly

Sources for Leukoencephalopathy, Cystic, Without Megalencephaly

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