NFLS
MCID: LGS001
MIFTS: 53

Legius Syndrome (NFLS) malady

Categories: Genetic diseases, Rare diseases, Skin diseases, Fetal diseases, Neuronal diseases

Aliases & Classifications for Legius Syndrome

Aliases & Descriptions for Legius Syndrome:

Name: Legius Syndrome 54 23 50 24 25 56 66 29 13
Neurofibromatosis Type 1-Like Syndrome 23 24 25
Nfls 24 25 66
Neurofibromatosis 1-Like Syndrome 56 66
Neurofibromatosis, Type 1-Like Syndrome 69
Neurofibromatosis Type 1 Like Syndrome 50
Cafe-Au-Lait Spots 42
Nf1-Like Syndrome 56

Characteristics:

Orphanet epidemiological data:

56
legius syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

GeneReviews:

23
legius syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance The vast majority of individuals with spred1 pathogenic variants have café au lait macules and/or freckling; however, the age of pigment penetrance is not established. only two individuals (a 60-year-old male and a 2-year-old child), each with a presumed spred1 pathogenic variant, were reported not to have café au lait macules or freckling [brems et al 2007, messiaen et al 2009]...

Classifications:



External Ids:

OMIM 54 611431
Orphanet 56 ORPHA137605
MESH via Orphanet 43 C548032
UMLS via Orphanet 70 C1969623
ICD10 via Orphanet 34 Q85.0
MedGen 40 C1969623
MeSH 42 D019080

Summaries for Legius Syndrome

OMIM : 54 Legius syndrome is an autosomal dominant disorder that shows some similarities to neurofibromatosis type I (NF1;... (611431) more...

MalaCards based summary : Legius Syndrome, also known as neurofibromatosis type 1-like syndrome, is related to cafe-au-lait spots, multiple and watson syndrome, and has symptoms including macrocephaly, hypertelorism and short neck. An important gene associated with Legius Syndrome is SPRED1 (Sprouty Related EVH1 Domain Containing 1), and among its related pathways/superpathways are Cytokine Signaling in Immune system and Negative regulation of FGFR1 signaling. The drugs Chlorhexidine and Lamotrigine have been mentioned in the context of this disorder. Affiliated tissues include skin, and related phenotypes are craniofacial and limbs/digits/tail

UniProtKB/Swiss-Prot : 66 Neurofibromatosis 1-like syndrome: A disorder characterized mainly by cafe au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1, axillary freckling, and macrocephaly. Additional clinical manifestations include Noonan-like facial dysmorphism, lipomas, learning disabilities and attention deficit-hyperactivity.

Genetics Home Reference : 25 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.

Wikipedia : 71 Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was... more...

GeneReviews: NBK47312

Related Diseases for Legius Syndrome

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

(show all 47)
id Related Disease Score Top Affiliating Genes
1 cafe-au-lait spots, multiple 12.6
2 watson syndrome 12.3
3 neurofibromatosis, type 1 11.2
4 noonan syndrome 1 10.8
5 pleural cancer 10.2 NF1 SPRED1
6 growth hormone insensitivity with immunodeficiency 10.2 NF1 PTPN11
7 vulvar apocrine adenocarcinoma 10.1 PTPN11 SPRED1
8 neurofibromatosis 10.1
9 syndactyly-polydactyly-earlobe syndrome 10.1 NF1 PTPN11
10 vulvar sebaceous carcinoma 10.1 PTPN11 SPRED1
11 papillary follicular thyroid adenocarcinoma 10.1 SPRY1 SPRY2
12 chromosome 15q11-q13 duplication syndrome 10.1 NF1 PTPN11 SPRED1
13 nephrolithiasis 10.1 NF1 PTPN11 SPRED1
14 skin epithelioid hemangioma 10.1 NF1 PTPN11
15 medullary cystic kidney disease 1 10.1 NF1 PTPN11 SPRED1
16 metachondromatosis 10.1 NF1 PTPN11 SPRED1
17 large intestine adenoma 9.9 MSH2 MSH6
18 benign fibrous mesothelioma 9.9 MSH2 MSH6
19 autoimmune autonomic ganglionopathy 9.9 MSH2 MSH6
20 neuropathy, distal hereditary motor, type viib 9.9 MSH2 MSH6
21 lateral sclerosis 9.9
22 churg-strauss syndrome 9.9 MSH2 MSH6
23 cauda equina neoplasm 9.8 MSH2 MSH6
24 autosomal genetic disease 9.8 MSH2 MSH6 NF1
25 neuronitis 9.8
26 encephalopathy 9.8
27 t-cell large granular lymphocyte leukemia 9.8 MSH2 MSH6 NF1
28 mismatch repair cancer syndrome 9.8 MSH2 MSH6
29 hnrnpa1-related amyotrophic lateral sclerosis 9.8 MSH2 MSH6
30 piebaldism 9.8
31 neuroretinitis 9.8 MSH2 MSH6
32 neurofibromatosis-noonan syndrome 9.7 MSH2 MSH6 NF1 SPRED1
33 fibromatosis, gingival, 1 9.7 MSH2 MSH6
34 subcortical arteriosclerotic encephalopathy 9.7
35 charcot-marie-tooth disease 9.7
36 hydrocephalus 9.7
37 tooth disease 9.7
38 normal pressure hydrocephalus 9.7
39 substance abuse 9.7
40 retinitis 9.7
41 craniopharyngioma 9.7
42 neuropathy 9.7
43 hiv-1 9.7
44 glioma 9.7
45 head injury 9.7
46 seborrheic dermatitis 9.5 MSH2 MSH6 NF1 PTPN11 SPRED1
47 cardiomyopathy, dilated, 1r 8.6 MSH2 MSH6 NF1 PTPN11 SPRED1 SPRED2

Graphical network of the top 20 diseases related to Legius Syndrome:



Diseases related to Legius Syndrome

Symptoms & Phenotypes for Legius Syndrome

Symptoms by clinical synopsis from OMIM:

611431

Clinical features from OMIM:

611431

Human phenotypes related to Legius Syndrome:

32 (show all 19)
id Description HPO Frequency HPO Source Accession
1 macrocephaly 32 HP:0000256
2 hypertelorism 32 HP:0000316
3 short neck 32 HP:0000470
4 ptosis 32 HP:0000508
5 muscular hypotonia 32 HP:0001252
6 micrognathia 32 HP:0000347
7 epicanthus 32 HP:0000286
8 attention deficit hyperactivity disorder 32 HP:0007018
9 low posterior hairline 32 HP:0002162
10 high, narrow palate 32 HP:0002705
11 multiple lipomas 32 HP:0001012
12 low-set, posteriorly rotated ears 32 HP:0000368
13 downslanted palpebral fissures 32 HP:0000494
14 specific learning disability 32 HP:0001328
15 triangular face 32 HP:0000325
16 abnormality of the sternum 32 HP:0000766
17 cafe-au-lait spot 32 HP:0000957
18 neurofibromas 32 HP:0001067
19 axillary freckling 32 HP:0000997

MGI Mouse Phenotypes related to Legius Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.65 SPRY2 SPRY4 NF1 PTPN11 SPRED1
2 limbs/digits/tail MP:0005371 9.63 NF1 PTPN11 SPRED1 SPRED2 SPRY2 SPRY4
3 neoplasm MP:0002006 9.43 MSH2 MSH6 NF1 PTPN11 SPRY1 SPRY2
4 respiratory system MP:0005388 9.02 NF1 PTPN11 SPRED1 SPRY2 SPRY4

Drugs & Therapeutics for Legius Syndrome

Drugs for Legius Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 33)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Chlorhexidine Approved, Vet_approved Phase 2, Phase 3 55-56-1 9552079 2713
2
Lamotrigine Approved, Investigational Phase 2, Phase 3 84057-84-1 3878
3 Anticonvulsants Phase 2, Phase 3
4 calcium channel blockers Phase 2, Phase 3
5 Calcium, Dietary Phase 2, Phase 3
6 Chlorhexidine gluconate Phase 2, Phase 3
7 Diuretics, Potassium Sparing Phase 2, Phase 3
8 Excitatory Amino Acid Antagonists Phase 2, Phase 3
9 Excitatory Amino Acids Phase 2, Phase 3
10 Neurotransmitter Agents Phase 2, Phase 3
11 Sodium Channel Blockers Phase 2, Phase 3
12
Lovastatin Approved, Investigational Phase 1 75330-75-5 53232
13
Letrozole Approved, Investigational Phase 1 112809-51-5 3902
14
alemtuzumab Approved, Investigational Phase 1 216503-57-0
15
Fludarabine Approved Phase 1 21679-14-1, 75607-67-9 30751
16 Anticholesteremic Agents Phase 1
17 Antimetabolites Phase 1
18 Dihydromevinolin Phase 1
19 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 1
20 Hypolipidemic Agents Phase 1
21 L 647318 Phase 1
22 Lipid Regulating Agents Phase 1
23 Aromatase Inhibitors Phase 1
24 Estrogen Antagonists Phase 1
25 Estrogens Phase 1
26 Hormone Antagonists Phase 1
27 Hormones Phase 1
28 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 1
29 Steroid Synthesis Inhibitors Phase 1
30 Antimetabolites, Antineoplastic Phase 1
31 Immunosuppressive Agents Phase 1
32 Neuroserpin
33 Astragalus Nutraceutical

Interventional clinical trials:

(show all 11)
id Name Status NCT ID Phase
1 Effect of Lamotrigine on Cognition in NF1 Recruiting NCT02256124 Phase 2, Phase 3
2 Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1) Completed NCT00352599 Phase 1
3 Effects of Letrozole on Precocious Puberty Due to McCune Albright Syndrome Completed NCT00006174 Phase 1
4 Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT Terminated NCT00586274 Phase 1
5 Genetic Disease Gene Identification Unknown status NCT00916903
6 Analysis of Peripheral Nerve Sheath Tumors (PNSTs) in Neurofibromatosis Type 1 (NF1) Patients Unknown status NCT01218139
7 Microarray CGH Analysis of Circulating Tumoral Plasma DNA in NF1 Patients With MPNSTs Unknown status NCT01218152
8 Genetic Evaluation of NF1 and Scoliosis Patients Completed NCT01776125
9 Natural History Study of Patients With Neurofibromatosis Type I Recruiting NCT00924196
10 Study of Disease Severity in Adults With Neurofibromatosis Type 1 (NF1) Active, not recruiting NCT00111384
11 Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Dermal Neurofibroma Not yet recruiting NCT02839720

Search NIH Clinical Center for Legius Syndrome

Cochrane evidence based reviews: cafe-au-lait spots

Genetic Tests for Legius Syndrome

Genetic tests related to Legius Syndrome:

id Genetic test Affiliating Genes
1 Legius Syndrome 29 24 SPRED1

Anatomical Context for Legius Syndrome

MalaCards organs/tissues related to Legius Syndrome:

39
Skin

Publications for Legius Syndrome

Articles related to Legius Syndrome:

(show all 23)
id Title Authors Year
1
The first Slovak Legius syndrome patient carrying the SPRED1 gene mutation. ( 28150585 )
2017
2
Legius syndrome: A case report. ( 28378438 )
2017
3
Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1. ( 26635368 )
2016
4
Legius syndrome: case report and review of literature. ( 25883013 )
2015
5
Legius Syndrome: two novel mutations in the SPRED1 gene. ( 27081556 )
2015
6
Family with Legius syndrome (neurofibromatosis type 1-like syndrome). ( 25981987 )
2015
7
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia. ( 24469042 )
2014
8
Legius Syndrome, an Update.Molecular Pathology of Mutations in SPRED1. ( 24334617 )
2013
9
CafAc-au-lait macules and intertriginous freckling in piebaldism: clinical overlap with neurofibromatosis type 1 and Legius syndrome. ( 22438235 )
2012
10
Review and update of SPRED1 mutations causing Legius syndrome. ( 22753041 )
2012
11
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. ( 22751498 )
2012
12
Observations on intelligence and behavior in 15 patients with Legius syndrome. ( 21495177 )
2011
13
Legius syndrome in fourteen families. ( 21089071 )
2011
14
The SPRED1 Variants Repository for Legius Syndrome. ( 22384355 )
2011
15
Identification of five novel SPRED1 germline mutations in Legius syndrome. ( 21649642 )
2011
16
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108386 )
2010
17
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108420 )
2010
18
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108385 )
2010
19
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108422 )
2010
20
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108421 )
2010
21
Pigmentary findings in neurofibromatosis type 1-like syndrome (Legius syndrome): potential diagnostic dilemmas. ( 19920242 )
2009
22
SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. ( 19443465 )
2009
23
Legius Syndrome ( 20945555 )
1993

Variations for Legius Syndrome

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

66
id Symbol AA change Variation ID SNP ID
1 SPRED1 p.Trp31Cys VAR_064827
2 SPRED1 p.Val44Asp VAR_064828 rs121434318

ClinVar genetic disease variations for Legius Syndrome:

6 (show all 15)
id Gene Variation Type Significance SNP ID Assembly Location
1 SPRED1 NM_152594.2(SPRED1): c.637C> T (p.Gln213Ter) single nucleotide variant Pathogenic rs121434316 GRCh38 Chromosome 15, 38349476: 38349476
2 SPRED1 NM_152594.2(SPRED1): c.784A> T (p.Arg262Ter) single nucleotide variant Pathogenic rs121434317 GRCh37 Chromosome 15, 38643314: 38643314
3 SPRED1 NM_152594.2(SPRED1): c.349C> T (p.Arg117Ter) single nucleotide variant Pathogenic rs121434312 GRCh37 Chromosome 15, 38614583: 38614583
4 SPRED1 NM_152594.2(SPRED1): c.70C> T (p.Arg24Ter) single nucleotide variant Pathogenic rs121434313 GRCh37 Chromosome 15, 38591611: 38591611
5 SPRED1 SPRED1, IVS5DS, G-A, +1 single nucleotide variant Pathogenic
6 SPRED1 NM_152594.2(SPRED1): c.643C> T (p.Gln215Ter) single nucleotide variant Pathogenic rs121434314 GRCh37 Chromosome 15, 38641683: 38641683
7 SPRED1 NM_152594.2(SPRED1): c.190C> T (p.Arg64Ter) single nucleotide variant Pathogenic rs121434315 GRCh37 Chromosome 15, 38591731: 38591731
8 SPRED1 NM_152594.2(SPRED1): c.131T> A (p.Val44Asp) single nucleotide variant Pathogenic rs121434318 GRCh37 Chromosome 15, 38591672: 38591672
9 SPRED1 SPRED1, 2-BP DEL, 1045AG deletion Pathogenic
10 NF1 NM_000267.3(NF1): c.2041C> T (p.Arg681Ter) single nucleotide variant Pathogenic rs768638173 GRCh38 Chromosome 17, 31226474: 31226474
11 SPRED1 NM_152594.2(SPRED1): c.796_797delAT (p.Met266Valfs) deletion Pathogenic rs864622410 GRCh38 Chromosome 15, 38351125: 38351126
12 SPRED1 NM_152594.2(SPRED1): c.1151_1152delAG (p.Glu384Glyfs) deletion Pathogenic rs878855228 GRCh37 Chromosome 15, 38643681: 38643682
13 SPRED1 NM_152594.2(SPRED1): c.973C> T (p.Arg325Ter) single nucleotide variant Pathogenic rs1057518683 GRCh37 Chromosome 15, 38643503: 38643503
14 SPRED1 NC_000015.10: g.(?_38299373)_(38357249_?)del deletion Pathogenic GRCh37 Chromosome 15, 38591574: 38649450
15 SPRED1 NM_152594.2(SPRED1): c.421C> T (p.Gln141Ter) single nucleotide variant Pathogenic rs1060502505 GRCh38 Chromosome 15, 38324807: 38324807

Copy number variations for Legius Syndrome from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 91538 15 31400000 37900000 Copy number SPRED1 Legius syndrome

Expression for Legius Syndrome

Search GEO for disease gene expression data for Legius Syndrome.

Pathways for Legius Syndrome

Pathways related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 11)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.97 NF1 PTPN11 SPRED1 SPRED2 SPRED3
2
Show member pathways
12.08 PTPN11 SPRED1 SPRED2 SPRY2
3
Show member pathways
11.79 PTPN11 SPRED1 SPRED2
4
Show member pathways
11.74 PTPN11 SPRED1 SPRED2 SPRY2
5 11.73 MSH2 MSH6 NF1
6 11.65 SPRED1 SPRY1 SPRY2
7
Show member pathways
11.38 NF1 SPRED1 SPRED2 SPRED3
8 11.17 PTPN11 SPRY2
9 11.14 MSH2 MSH6
10 10.96 NF1 PTPN11 SPRY1 SPRY2
11 10.9 MSH2 MSH6

GO Terms for Legius Syndrome

Cellular components related to Legius Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 MutSalpha complex GO:0032301 8.62 MSH2 MSH6

Biological processes related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 26)
id Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.8 SPRED1 SPRED2 SPRED3 SPRY1 SPRY2 SPRY3
2 fibroblast growth factor receptor signaling pathway GO:0008543 9.71 PTPN11 SPRED1 SPRED2
3 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008630 9.63 MSH2 MSH6
4 negative regulation of ERK1 and ERK2 cascade GO:0070373 9.63 SPRY1 SPRY2 SPRY4
5 negative regulation of GTPase activity GO:0034260 9.62 SPRY1 SPRY2
6 mismatch repair GO:0006298 9.62 MSH2 MSH6
7 negative regulation of epidermal growth factor receptor signaling pathway GO:0042059 9.61 SPRY1 SPRY2
8 metanephros development GO:0001656 9.61 NF1 SPRY1
9 inactivation of MAPK activity GO:0000188 9.6 SPRED1 SPRED2
10 establishment of mitotic spindle orientation GO:0000132 9.59 SPRY1 SPRY2
11 isotype switching GO:0045190 9.58 MSH2 MSH6
12 somatic hypermutation of immunoglobulin genes GO:0016446 9.58 MSH2 MSH6
13 determination of adult lifespan GO:0008340 9.57 MSH2 MSH6
14 positive regulation of DNA damage response, signal transduction by p53 class mediator GO:0043517 9.56 SPRED1 SPRED2
15 negative regulation of fibroblast growth factor receptor signaling pathway GO:0040037 9.55 SPRY1 SPRY2
16 bud elongation involved in lung branching GO:0060449 9.52 SPRY1 SPRY2
17 negative regulation of DNA recombination GO:0045910 9.51 MSH2 MSH6
18 negative regulation of Ras protein signal transduction GO:0046580 9.5 NF1 SPRY1 SPRY2
19 positive regulation of helicase activity GO:0051096 9.49 MSH2 MSH6
20 maintenance of DNA repeat elements GO:0043570 9.48 MSH2 MSH6
21 somatic recombination of immunoglobulin gene segments GO:0016447 9.43 MSH2 MSH6
22 negative regulation of neurotrophin TRK receptor signaling pathway GO:0051387 9.4 SPRY1 SPRY2
23 regulation of protein deacetylation GO:0090311 9.37 SPRED1 SPRED2
24 negative regulation of peptidyl-threonine phosphorylation GO:0010801 9.33 SPRED1 SPRED2 SPRY2
25 negative regulation of MAP kinase activity GO:0043407 9.26 NF1 SPRY1 SPRY2 SPRY4
26 regulation of signal transduction GO:0009966 9.17 SPRED1 SPRED2 SPRED3 SPRY1 SPRY2 SPRY3

Molecular functions related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 11)
id Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 9.78 MSH2 SPRED1 SPRED2 SPRY2
2 ADP binding GO:0043531 9.49 MSH2 MSH6
3 four-way junction DNA binding GO:0000400 9.46 MSH2 MSH6
4 mismatched DNA binding GO:0030983 9.43 MSH2 MSH6
5 oxidized purine DNA binding GO:0032357 9.4 MSH2 MSH6
6 MutLalpha complex binding GO:0032405 9.37 MSH2 MSH6
7 guanine/thymine mispair binding GO:0032137 9.32 MSH2 MSH6
8 single guanine insertion binding GO:0032142 9.26 MSH2 MSH6
9 stem cell factor receptor binding GO:0005173 9.16 SPRED1 SPRED2
10 single thymine insertion binding GO:0032143 8.96 MSH2 MSH6
11 protein serine/threonine kinase inhibitor activity GO:0030291 8.8 SPRED1 SPRED2 SPRY2

Sources for Legius Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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