LKPAT
MCID: LKN017
MIFTS: 28

Leukoencephalopathy with Ataxia (LKPAT)

Categories: Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leukoencephalopathy with Ataxia

MalaCards integrated aliases for Leukoencephalopathy with Ataxia:

Name: Leukoencephalopathy with Ataxia 57 72 29 6 39 70
Lkpat 57 72
Leukoencephalopathy with Mild Cerebellar Ataxia and White Matter Edema 58

Characteristics:

Orphanet epidemiological data:

58
leukoencephalopathy with mild cerebellar ataxia and white matter edema
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
two peaks of onset, childhood and adult
variable clinical features


HPO:

31
leukoencephalopathy with ataxia:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM® 57 615651
ICD10 via Orphanet 33 E75.2
Orphanet 58 ORPHA363540
UMLS 70 C3810242

Summaries for Leukoencephalopathy with Ataxia

OMIM® : 57 Leukoencephalopathy with ataxia is an autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient (ADC) values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles. The findings suggest myelin microvacuolation restricted to certain brain regions. Clinical features include ataxia and unstable gait; more variable abnormalities may include visual field defects, headaches, and learning disabilities (summary by Depienne et al., 2013). (615651) (Updated 20-May-2021)

MalaCards based summary : Leukoencephalopathy with Ataxia, also known as lkpat, is related to clcn2-related leukoencephalopathy and ataxia and polyneuropathy, adult-onset, and has symptoms including headache and gait ataxia. An important gene associated with Leukoencephalopathy with Ataxia is CLCN2 (Chloride Voltage-Gated Channel 2). Affiliated tissues include pons, eye and brain, and related phenotypes are optic neuropathy and visual field defect

UniProtKB/Swiss-Prot : 72 Leukoencephalopathy with ataxia: An autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles, suggesting myelin microvacuolation. Clinical features include ataxia and unstable gait. More variable abnormalities may include visual field defects, headaches, and learning disabilities.

Related Diseases for Leukoencephalopathy with Ataxia

Diseases related to Leukoencephalopathy with Ataxia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 clcn2-related leukoencephalopathy 11.3
2 ataxia and polyneuropathy, adult-onset 10.0
3 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 9.9
4 polr3-related leukodystrophy 9.9

Symptoms & Phenotypes for Leukoencephalopathy with Ataxia

Human phenotypes related to Leukoencephalopathy with Ataxia:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 optic neuropathy 31 occasional (7.5%) HP:0001138
2 visual field defect 31 occasional (7.5%) HP:0001123
3 abnormal chorioretinal morphology 31 occasional (7.5%) HP:0000532
4 headache 31 HP:0002315
5 gait ataxia 31 HP:0002066
6 leukoencephalopathy 31 HP:0002352
7 limb ataxia 31 HP:0002070

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
headache
gait ataxia
leukoencephalopathy
limb ataxia
learning disabilities (in some patients)
more
Head And Neck Eyes:
visual field defects (in some patients)
chorioretinopathy (in some patients)
optic neuropathy (in some patients)

Clinical features from OMIM®:

615651 (Updated 20-May-2021)

UMLS symptoms related to Leukoencephalopathy with Ataxia:


headache; gait ataxia

Drugs & Therapeutics for Leukoencephalopathy with Ataxia

Search Clinical Trials , NIH Clinical Center for Leukoencephalopathy with Ataxia

Genetic Tests for Leukoencephalopathy with Ataxia

Genetic tests related to Leukoencephalopathy with Ataxia:

# Genetic test Affiliating Genes
1 Leukoencephalopathy with Ataxia 29 CLCN2

Anatomical Context for Leukoencephalopathy with Ataxia

MalaCards organs/tissues related to Leukoencephalopathy with Ataxia:

40
Pons, Eye, Brain

Publications for Leukoencephalopathy with Ataxia

Articles related to Leukoencephalopathy with Ataxia:

# Title Authors PMID Year
1
Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. 6 57
23707145 2013
2
Secondary paroxysmal kinesigenic dyskinesia associated with CLCN2 gene mutation. 6
25745790 2015
3
Subclinical leukodystrophy and infertility in a man with a novel homozygous CLCN2 mutation. 6
25128180 2014
4
Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. 6
21703448 2011
5
Leukoencephalopathy upon disruption of the chloride channel ClC-2. 57
17567819 2007
6
Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. 6
12612585 2003
7
Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption. 57
11250895 2001
8
A novel homozygous change of CLCN2 (p.His590Pro) is associated with a subclinical form of leukoencephalopathy with ataxia (LKPAT). 61
28473625 2017
9
Assessment of myelination in hypomyelinating disorders by quantitative MRI. 61
22911904 2012
10
Leukoencephalopathy with ataxia, hypodontia, and hypomyelination. 61
15851747 2005

Variations for Leukoencephalopathy with Ataxia

ClinVar genetic disease variations for Leukoencephalopathy with Ataxia:

6 (show all 43)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLCN2 NM_004366.6(CLCN2):c.828dup (p.Arg277fs) Duplication Pathogenic 100632 rs587777112 GRCh37: 3:184075219-184075220
GRCh38: 3:184357431-184357432
2 CLCN2 NM_004366.6(CLCN2):c.1143del (p.Gly382fs) Deletion Pathogenic 217788 rs863225252 GRCh37: 3:184073509-184073509
GRCh38: 3:184355721-184355721
3 CLCN2 NM_004366.6(CLCN2):c.1113delinsACTGCTCAT (p.Ser375fs) Indel Pathogenic 217787 rs863225251 GRCh37: 3:184073539-184073539
GRCh38: 3:184355751-184355751
4 CLCN2 NM_004366.6(CLCN2):c.64-1107_639del Deletion Pathogenic 217783 GRCh37: 3:184075621-184078026
GRCh38: 3:184357833-184360238
5 CLCN2 NM_004366.6(CLCN2):c.1397-1G>A SNV Pathogenic 813301 rs1478304584 GRCh37: 3:184072447-184072447
GRCh38: 3:184354659-184354659
6 CLCN2 NM_004366.6(CLCN2):c.2134_2135del (p.Pro713fs) Microsatellite Pathogenic 1032900 GRCh37: 3:184070829-184070830
GRCh38: 3:184353041-184353042
7 CLCN2 NM_004366.6(CLCN2):c.985_986del (p.Ile329fs) Deletion Pathogenic 1032901 GRCh37: 3:184074880-184074881
GRCh38: 3:184357092-184357093
8 CLCN2 NM_004366.6(CLCN2):c.1709G>A (p.Trp570Ter) SNV Pathogenic 100629 rs201330912 GRCh37: 3:184071901-184071901
GRCh38: 3:184354113-184354113
9 CLCN2 NM_004366.6(CLCN2):c.430_435del (p.Leu144_Ile145del) Deletion Pathogenic 100630 rs587777110 GRCh37: 3:184076016-184076021
GRCh38: 3:184358228-184358233
10 CLCN2 NM_004366.6(CLCN2):c.1499C>T (p.Ala500Val) SNV Pathogenic 100631 rs587777111 GRCh37: 3:184072344-184072344
GRCh38: 3:184354556-184354556
11 CLCN2 NM_004366.6(CLCN2):c.1304del (p.Leu435fs) Deletion Pathogenic 217789 rs863225253 GRCh37: 3:184073184-184073184
GRCh38: 3:184355396-184355396
12 CLCN2 NM_004366.6(CLCN2):c.1422_1423del (p.Glu475fs) Deletion Pathogenic 217792 rs863225255 GRCh37: 3:184072420-184072421
GRCh38: 3:184354632-184354633
13 CLCN2 NM_004366.6(CLCN2):c.925C>T (p.Arg309Ter) SNV Pathogenic 217785 rs863225250 GRCh37: 3:184075028-184075028
GRCh38: 3:184357240-184357240
14 CLCN2 NM_004366.6(CLCN2):c.1507G>A (p.Gly503Arg) SNV Pathogenic 217793 rs777105668 GRCh37: 3:184072336-184072336
GRCh38: 3:184354548-184354548
15 CLCN2 NM_004366.6(CLCN2):c.1957A>T (p.Arg653Ter) SNV Pathogenic 217795 rs863225256 GRCh37: 3:184071109-184071109
GRCh38: 3:184353321-184353321
16 CLCN2 NM_004366.6(CLCN2):c.1412G>A (p.Arg471His) SNV Pathogenic 217791 rs771507094 GRCh37: 3:184072431-184072431
GRCh38: 3:184354643-184354643
17 CLCN2 NM_004366.6(CLCN2):c.2386C>T (p.Gln796Ter) SNV Pathogenic 217796 rs376823689 GRCh37: 3:184069830-184069830
GRCh38: 3:184352042-184352042
18 CLCN2 NM_004366.6(CLCN2):c.1397G>A (p.Gly466Glu) SNV Pathogenic 217790 rs863225254 GRCh37: 3:184072446-184072446
GRCh38: 3:184354658-184354658
19 CLCN2 NM_004366.6(CLCN2):c.1015G>C (p.Val339Leu) SNV Pathogenic 217786 rs532632165 GRCh37: 3:184074851-184074851
GRCh38: 3:184357063-184357063
20 CLCN2 NM_004366.6(CLCN2):c.292G>C (p.Gly98Arg) SNV Pathogenic 217784 rs863225249 GRCh37: 3:184076530-184076530
GRCh38: 3:184358742-184358742
21 CLCN2 NM_004366.6(CLCN2):c.1795G>A (p.Asp599Asn) SNV Pathogenic 217794 rs141242566 GRCh37: 3:184071510-184071510
GRCh38: 3:184353722-184353722
22 CLCN2 NM_004366.6(CLCN2):c.597dup (p.Met200fs) Duplication Likely pathogenic 9035 rs515726131 GRCh37: 3:184075767-184075768
GRCh38: 3:184357979-184357980
23 CLCN2 NM_004366.6(CLCN2):c.704G>A (p.Arg235Gln) SNV Uncertain significance 9038 rs71318369 GRCh37: 3:184075476-184075476
GRCh38: 3:184357688-184357688
24 CLCN2 NM_004366.6(CLCN2):c.596G>C (p.Gly199Ala) SNV Uncertain significance 217772 rs863225248 GRCh37: 3:184075769-184075769
GRCh38: 3:184357981-184357981
25 CLCN2 NM_004366.6(CLCN2):c.2154G>C (p.Glu718Asp) SNV Uncertain significance 217778 rs2228292 GRCh37: 3:184070588-184070588
GRCh38: 3:184352800-184352800
26 CLCN2 NM_004366.6(CLCN2):c.704G>A (p.Arg235Gln) SNV Uncertain significance 9038 rs71318369 GRCh37: 3:184075476-184075476
GRCh38: 3:184357688-184357688
27 CLCN2 NM_004366.6(CLCN2):c.1930C>T (p.Arg644Cys) SNV Uncertain significance 217774 rs148545588 GRCh37: 3:184071136-184071136
GRCh38: 3:184353348-184353348
28 CLCN2 NM_004366.6(CLCN2):c.2279C>T (p.Ala760Val) SNV Uncertain significance 217782 rs781034991 GRCh37: 3:184070112-184070112
GRCh38: 3:184352324-184352324
29 CLCN2 NM_004366.6(CLCN2):c.2003C>G (p.Thr668Ser) SNV Uncertain significance 217776 rs9820367 GRCh37: 3:184071063-184071063
GRCh38: 3:184353275-184353275
30 CLCN2 NM_004366.6(CLCN2):c.2273G>A (p.Ser758Asn) SNV Uncertain significance 217781 rs753380048 GRCh37: 3:184070118-184070118
GRCh38: 3:184352330-184352330
31 CLCN2 NM_004366.6(CLCN2):c.246C>G (p.Phe82Leu) SNV Uncertain significance 217771 rs140463309 GRCh37: 3:184076576-184076576
GRCh38: 3:184358788-184358788
32 CLCN2 NM_004366.6(CLCN2):c.143C>G (p.Pro48Arg) SNV Uncertain significance 217768 rs115661422 GRCh37: 3:184076840-184076840
GRCh38: 3:184359052-184359052
33 CLCN2 NM_004366.6(CLCN2):c.130G>A (p.Gly44Arg) SNV Uncertain significance 217767 rs863225247 GRCh37: 3:184076853-184076853
GRCh38: 3:184359065-184359065
34 CLCN2 NM_004366.6(CLCN2):c.218G>A (p.Arg73His) SNV Uncertain significance 217770 rs144412275 GRCh37: 3:184076765-184076765
GRCh38: 3:184358977-184358977
35 CLCN2 NM_004366.6(CLCN2):c.1937G>A (p.Arg646Gln) SNV Uncertain significance 217775 rs115961753 GRCh37: 3:184071129-184071129
GRCh38: 3:184353341-184353341
36 CLCN2 NM_004366.6(CLCN2):c.2144G>A (p.Gly715Glu) SNV Uncertain significance 9037 rs137852681 GRCh37: 3:184070598-184070598
GRCh38: 3:184352810-184352810
37 CLCN2 NM_004366.6(CLCN2):c.1856-3C>T SNV Uncertain significance 217773 rs371193424 GRCh37: 3:184071213-184071213
GRCh38: 3:184353425-184353425
38 CLCN2 NM_004366.6(CLCN2):c.1730G>A (p.Arg577Gln) SNV Uncertain significance 9039 rs137852682 GRCh37: 3:184071575-184071575
GRCh38: 3:184353787-184353787
39 CLCN2 NM_004366.6(CLCN2):c.203G>A (p.Arg68His) SNV Uncertain significance 217769 rs61729156 GRCh37: 3:184076780-184076780
GRCh38: 3:184358992-184358992
40 CLCN2 NM_004366.6(CLCN2):c.2063G>A (p.Arg688Gln) SNV Uncertain significance 217777 rs111656822 GRCh37: 3:184070901-184070901
GRCh38: 3:184353113-184353113
41 CLCN2 NM_004366.6(CLCN2):c.2173C>T (p.Arg725Trp) SNV Uncertain significance 217779 rs114702742 GRCh37: 3:184070569-184070569
GRCh38: 3:184352781-184352781
42 CLCN2 NM_004366.6(CLCN2):c.2240G>A (p.Arg747His) SNV Uncertain significance 217780 rs144164281 GRCh37: 3:184070262-184070262
GRCh38: 3:184352474-184352474
43 CLCN2 NM_004366.6(CLCN2):c.221-14_221-4del Deletion Uncertain significance 9036 rs515726132 GRCh37: 3:184076605-184076615
GRCh38: 3:184358817-184358827

UniProtKB/Swiss-Prot genetic disease variations for Leukoencephalopathy with Ataxia:

72
# Symbol AA change Variation ID SNP ID
1 CLCN2 p.Ala500Val VAR_070977 rs587777111

Expression for Leukoencephalopathy with Ataxia

Search GEO for disease gene expression data for Leukoencephalopathy with Ataxia.

Pathways for Leukoencephalopathy with Ataxia

GO Terms for Leukoencephalopathy with Ataxia

Sources for Leukoencephalopathy with Ataxia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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