NFLS
MCID: LGS001
MIFTS: 48

Legius Syndrome (NFLS) malady

Genetic diseases, Rare diseases, Skin diseases, Fetal diseases, Neuronal diseases categories
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Summaries for Legius Syndrome

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Genetics Home Reference:21 Legius syndrome is a condition characterized by changes in skin coloring (pigmentation). Almost all affected individuals have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals.

MalaCards based summary: Legius Syndrome, also known as neurofibromatosis type 1-like syndrome, is related to neurofibromatosis and amyotrophic lateral sclerosis, and has symptoms including An important gene associated with Legius Syndrome is SPRED1 (sprouty-related, EVH1 domain containing 1), and among its related pathways are Kit Receptor Signaling Pathway and Prostate cancer. Affiliated tissues include skin, and related mouse phenotypes are craniofacial and respiratory system.

Wikipedia:65 Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was... more...

Description from OMIM:46 611431

GeneReviews summary for legius

Aliases & Classifications for Legius Syndrome

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Sources:
62UMLS, 19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 46OMIM, 48Orphanet, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Legius Syndrome, Aliases & Descriptions:

Name: Legius Syndrome 19 42 20 22 21 46 48
Neurofibromatosis Type 1-Like Syndrome 19 21 62
Neurofibromatosis, Type 1-Like Syndrome 62
Neurofibromatosis Type 1 Like Syndrome 42
 
Neurofibromatosis 1-Like Syndrome 48
Neurofibromatosis 1 62
Nf1-Like Syndrome 48
Nfls 21


Classifications:



Characteristics (Orphanet epidemiological data):

48
legius syndrome:
Inheritance: Autosomal dominant; Age of onset: Neonatal/infancy; Age of death: Normal


External Ids:

OMIM46 611431
MESH via Orphanet35 C548032
ICD10 via Orphanet26 Q85.0
UMLS via Orphanet63 C1969623

Related Diseases for Legius Syndrome

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Diseases related to Legius Syndrome via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 16)
idRelated DiseaseScoreTop Affiliating Genes
1neurofibromatosis30.7NF1, SPRED1
2amyotrophic lateral sclerosis10.2
3lateral sclerosis10.2
4neuronitis10.2
5piebaldism10.1
6charcot-marie-tooth disease10.0
7hiv-110.0
8hydrocephalus10.0
9normal pressure hydrocephalus10.0
10craniopharyngioma10.0
11retinitis10.0
12tauopathy10.0
13tooth disease10.0
14head injury10.0
15subcortical arteriosclerotic encephalopathy10.0
16lumbar disc herniation10.0

Graphical network of diseases related to Legius Syndrome:



Diseases related to legius syndrome

Symptoms for Legius Syndrome

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Symptoms by clinical synopsis from OMIM:

611431

Clinical features from OMIM:

611431

HPO human phenotypes related to Legius Syndrome:

(show all 19)
id Description Frequency HPO Source Accession
1 abnormality of the sternum rare (5%) HP:0000766
2 autosomal dominant inheritance HP:0000006
3 high palate HP:0000218
4 macrocephaly HP:0000256
5 epicanthus HP:0000286
6 hypertelorism HP:0000316
7 triangular face HP:0000325
8 micrognathia HP:0000347
9 low-set, posteriorly rotated ears HP:0000368
10 short neck HP:0000470
11 downslanted palpebral fissures HP:0000494
12 ptosis HP:0000508
13 cafe-au-lait spot HP:0000957
14 axillary freckling HP:0000997
15 multiple lipomas HP:0001012
16 neurofibromas HP:0001067
17 specific learning disability HP:0001328
18 low posterior hairline HP:0002162
19 attention deficit hyperactivity disorder HP:0007018

Drugs & Therapeutics for Legius Syndrome

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Drug clinical trials:

Search ClinicalTrials for Legius Syndrome

Search NIH Clinical Center for Legius Syndrome

Genetic Tests for Legius Syndrome

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Genetic tests related to Legius Syndrome:

id Genetic test Affiliating Genes
1 Legius Syndrome20 22 SPRED1

Anatomical Context for Legius Syndrome

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MalaCards organs/tissues related to Legius Syndrome:

32
Skin

Animal Models for Legius Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Legius Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053828.8SPRY4, SPRED1, SPRY2, NF1
2MP:00053888.6SPRY4, SPRED1, SPRY2, NF1
3MP:00053718.4NF1, SPRY2, SPRED1, SPRED2, SPRY4
4MP:00053788.4NF1, SPRY2, SPRED1, SPRED2, SPRY4

Publications for Legius Syndrome

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Articles related to Legius Syndrome:

(show all 17)
idTitleAuthorsYear
1
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia. (24469042)
2014
2
Legius Syndrome, an Update.Molecular Pathology of Mutations in SPRED1. (24334617)
2013
3
Review and update of SPRED1 mutations causing Legius syndrome. (22753041)
2012
4
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. (22751498)
2012
5
CafAc-au-lait macules and intertriginous freckling in piebaldism: clinical overlap with neurofibromatosis type 1 and Legius syndrome. (22438235)
2012
6
Legius syndrome in fourteen families. (21089071)
2011
7
Identification of five novel SPRED1 germline mutations in Legius syndrome. (21649642)
2011
8
The SPRED1 Variants Repository for Legius Syndrome. (22384355)
2011
9
Observations on intelligence and behavior in 15 patients with Legius syndrome. (21495177)
2011
10
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. (20108421)
2010
11
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. (20108385)
2010
12
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. (20108422)
2010
13
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. (20108386)
2010
14
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. (20108420)
2010
15
SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. (19443465)
2009
16
Pigmentary findings in neurofibromatosis type 1-like syndrome (Legius syndrome): potential diagnostic dilemmas. (19920242)
2009
17
Legius Syndrome (20945555)
1993

Variations for Legius Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Legius Syndrome:

64
id Symbol AA change Variation ID SNP ID
1SPRED1p.Trp31CysVAR_064827
2SPRED1p.Val44AspVAR_064828

Clinvar genetic disease variations for Legius Syndrome:

6 (show all 34)
id Gene Name Type Significance SNP ID Assembly Location
1SPRED1NM_152594.2(SPRED1): c.349C> T (p.Arg117Ter)single nucleotide variantPathogenicrs121434312GRCh37Chr 15, 38614583: 38614583
2SPRED1NM_152594.2(SPRED1): c.70C> T (p.Arg24Ter)single nucleotide variantPathogenicrs121434313GRCh37Chr 15, 38591611: 38591611
3SPRED1SPRED1, IVS5DS, G-A, +1single nucleotide variantPathogenic
4SPRED1NM_152594.2(SPRED1): c.643C> T (p.Gln215Ter)single nucleotide variantPathogenicrs121434314GRCh37Chr 15, 38641683: 38641683
5SPRED1NM_152594.2(SPRED1): c.190C> T (p.Arg64Ter)single nucleotide variantPathogenicrs121434315GRCh37Chr 15, 38591731: 38591731
6SPRED1NM_152594.2(SPRED1): c.637C> T (p.Gln213Ter)single nucleotide variantPathogenicrs121434316GRCh37Chr 15, 38641677: 38641677
7SPRED1NM_152594.2(SPRED1): c.784A> T (p.Arg262Ter)single nucleotide variantPathogenicrs121434317GRCh37Chr 15, 38643314: 38643314
8SPRED1NM_152594.2(SPRED1): c.131T> A (p.Val44Asp)single nucleotide variantPathogenicrs121434318GRCh37Chr 15, 38591672: 38591672
9SPRED1SPRED1, 2-BP DEL, 1045AGdeletionPathogenic
10NF1NM_000267.3(NF1): c.5845A> T (p.Arg1949Ter)single nucleotide variantPathogenicrs267606595GRCh37Chr 17, 29661951: 29661951
11NF1NM_000267.3(NF1): c.4267A> G (p.Lys1423Glu)single nucleotide variantPathogenicrs137854550GRCh37Chr 17, 29585518: 29585518
12NF1NM_000267.3(NF1): c.5448dupC (p.Ser1817Leufs)duplicationPathogenicrs267606596GRCh37Chr 17, 29654759: 29654760
13NF1NM_000267.3(NF1): c.5465_5466insT (p.Lys1823Glnfs)insertionPathogenicrs267606597GRCh37Chr 17, 29654776: 29654777
14NF1NM_000267.3(NF1): c.6427C> A (p.Leu2143Met)single nucleotide variantPathogenicrs137854551GRCh37Chr 17, 29664448: 29664448
15NF1NM_000267.3(NF1): c.6511T> A (p.Tyr2171Asn)single nucleotide variantPathogenicrs267606598GRCh37Chr 17, 29664532: 29664532
16NF1NM_000267.3(NF1): c.5839C> T (p.Arg1947Ter)single nucleotide variantPathogenicrs137854552GRCh37Chr 17, 29661945: 29661945
17NF1NM_000267.3(NF1): c.4084C> T (p.Arg1362Ter)single nucleotide variantPathogenicrs137854560GRCh37Chr 17, 29576111: 29576111
18NF1NM_000267.3(NF1): c.3113+1G> Asingle nucleotide variantPathogenicrs267606599GRCh37Chr 17, 29557401: 29557401
19NF1NM_000267.3(NF1): c.1541_1542delAG (p.Gln514Argfs)deletionPathogenicrs267606600GRCh37Chr 17, 29546036: 29546037
20NF1NM_000267.3(NF1): c.3104T> G (p.Met1035Arg)single nucleotide variantPathogenicrs137854553GRCh37Chr 17, 29557391: 29557391
21NF1NM_000267.3(NF1): c.4173A> T (p.Arg1391Ser)single nucleotide variantPathogenicrs137854554GRCh37Chr 17, 29585424: 29585424
22NF1NM_000267.3(NF1): c.3827G> C (p.Arg1276Pro)single nucleotide variantPathogenicrs137854556GRCh37Chr 17, 29562747: 29562747
23NF1NM_000267.3(NF1): c.1466A> G (p.Tyr489Cys)single nucleotide variantPathogenicrs137854557GRCh37Chr 17, 29541542: 29541542
24NF1NM_000267.3(NF1): c.1523T> C (p.Leu508Pro)single nucleotide variantPathogenicrs137854558GRCh37Chr 17, 29541599: 29541599
25NF1NM_000267.3(NF1): c.1260+1G> Asingle nucleotide variantPathogenicrs267606603GRCh37Chr 17, 29528504: 29528504
26NF1NM_000267.3(NF1): c.4021C> T (p.Gln1341Ter)single nucleotide variantPathogenicrs137854559GRCh37Chr 17, 29576048: 29576048
27NF1NM_000267.3(NF1): c.5944-5A> Gsingle nucleotide variantPathogenicrs267606604GRCh37Chr 17, 29663346: 29663346
28NF1NM_000267.3(NF1): c.3721C> T (p.Arg1241Ter)single nucleotide variantPathogenicrs137854562GRCh37Chr 17, 29562641: 29562641
29NF1NM_000267.3(NF1): c.5406dupT (p.Ile1803Tyrfs)duplicationPathogenicrs267606605GRCh37Chr 17, 29654717: 29654718
30NF1NM_000267.3(NF1): c.1070T> C (p.Leu357Pro)single nucleotide variantPathogenicrs137854563GRCh37Chr 17, 29528062: 29528062
31NF1NM_000267.3(NF1): c.3728T> C (p.Leu1243Pro)single nucleotide variantPathogenicrs137854564GRCh37Chr 17, 29562648: 29562648
32NF1NM_000267.3(NF1): c.5710G> T (p.Glu1904Ter)single nucleotide variantPathogenicrs137854565GRCh37Chr 17, 29657477: 29657477
33NF1NM_000267.3(NF1): c.2531T> G (p.Leu844Arg)single nucleotide variantPathogenicrs137854566GRCh37Chr 17, 29556164: 29556164
34NF1NM_000267.3(NF1): c.574C> T (p.Arg192Ter)single nucleotide variantPathogenicrs397514641GRCh37Chr 17, 29497003: 29497003

Expression for genes affiliated with Legius Syndrome

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Expression patterns in normal tissues for genes affiliated with Legius Syndrome

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Pathways for genes affiliated with Legius Syndrome

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Pathways related to Legius Syndrome according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
Signaling events mediated by Stem cell factor receptor (c-Kit)37
9.6SPRED1, SPRED2
2
Show member pathways
Prostate Cancer37
Integrated Cancer pathway37
Steroid Biosynthesis37
9.5SPRY2, SPRY1
39.5SPRY1, SPRY2
4
Show member pathways
Type III interferon signaling37
7.4SPRY2, SPRED1, SPRED2, SPRY1, SPRED3, SPRY4

Compounds for genes affiliated with Legius Syndrome

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GO Terms for genes affiliated with Legius Syndrome

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Cellular components related to Legius Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1ruffle membraneGO:0325879.6SPRY2, SPRY4

Biological processes related to Legius Syndrome according to GeneCards/GeneDecks:

(show all 13)
idNameGO IDScoreTop Affiliating Genes
1regulation of protein deacetylationGO:0903119.8SPRED1, SPRED2
2negative regulation of Ras GTPase activityGO:0342619.7SPRY2, SPRY1
3negative regulation of neurotrophin TRK receptor signaling pathwayGO:0513879.7SPRY2, SPRY1
4positive regulation of DNA damage response, signal transduction by p53 class mediatorGO:0435179.6SPRED1, SPRED2
5negative regulation of fibroblast growth factor receptor signaling pathwayGO:0400379.6SPRY1, SPRY2
6negative regulation of epidermal growth factor receptor signaling pathwayGO:0420599.5SPRY2, SPRY1
7metanephros developmentGO:0016569.5NF1, SPRY1
8negative regulation of peptidyl-threonine phosphorylationGO:0108019.5SPRY2, SPRED1, SPRED2
9negative regulation of Ras protein signal transductionGO:0465809.4SPRY1, SPRY2, NF1
10negative regulation of ERK1 and ERK2 cascadeGO:0703739.2SPRY2, SPRY1
11inactivation of MAPK activityGO:0001889.0SPRED3, SPRED2, SPRED1
12negative regulation of MAP kinase activityGO:0434079.0NF1, SPRY2, SPRY1, SPRY4
13multicellular organismal developmentGO:0072758.2SPRED1, SPRED2, SPRED3, SPRY4, SPRY3

Molecular functions related to Legius Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1stem cell factor receptor bindingGO:0051739.3SPRED1, SPRED2
2protein kinase bindingGO:0199019.2SPRY2, SPRED1, SPRED2
3protein serine/threonine kinase inhibitor activityGO:0302919.1SPRY2, SPRED1, SPRED2

Products for genes affiliated with Legius Syndrome

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Sources for Legius Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet