MCID: MLN065
MIFTS: 49

Melanocytic Nevus Syndrome, Congenital

Categories: Genetic diseases, Skin diseases, Rare diseases

Aliases & Classifications for Melanocytic Nevus Syndrome, Congenital

MalaCards integrated aliases for Melanocytic Nevus Syndrome, Congenital:

Name: Melanocytic Nevus Syndrome, Congenital 57 75
Giant Pigmented Hairy Nevus 57 76 59 75 40 73
Giant Congenital Pigmented Nevus 57 75
Pigmented Moles 57 75
Nevus Spilus 75 73
Lentigo 44 73
Cmns 57 75
Gphn 57 75
Melanocytic Nevus Syndrome, Congenital, Somatic 57
Spitz Nevus or Nevus Spilus, Somatic 57
Nevus, Spindle Cell and Epithelioid 75
Nevus, Epithelioid and Spindle Cell 44
Giant Congenital Melanocytic Nevus 59
Large Congenital Melanocytic Nevus 59
Spindle Cell and Epithelioid Nevus 75
Epithelioid and Spindle Cell Nevus 73
Giant Pigmented Hairy Nevus; Gphn 57
Congenital Melanocytic Nevus 73
Congenital Pigmented Nevus 59
Speckled Lentiginous Nevus 75
Melanocytic Nevus of Skin 73
Melanocytic Nevus 73
Nevus, Pigmented 44
Nevoid Lentigo 75
Nevus, Spitz 75
Spitz Nevus 75
Nevuspi 75
Spitzn 75
Lcmn 59
Gmn 59

Characteristics:

Orphanet epidemiological data:

59
large congenital melanocytic nevus
Prevalence: 1-9/100000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth
relatives with multiple small congenital pigmented nevi


HPO:

32
melanocytic nevus syndrome, congenital:
Onset and clinical course congenital onset
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare skin diseases


External Ids:

OMIM 57 137550
Orphanet 59 ORPHA626
UMLS via Orphanet 74 C1318558 C1842036
ICD10 via Orphanet 34 Q82.5

Summaries for Melanocytic Nevus Syndrome, Congenital

OMIM : 57 Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012). Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by Sarin et al., 2013). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by Sarin et al., 2014). (137550)

MalaCards based summary : Melanocytic Nevus Syndrome, Congenital, also known as giant pigmented hairy nevus, is related to giant congenital nevus and nevus, epidermal. An important gene associated with Melanocytic Nevus Syndrome, Congenital is NRAS (NRAS Proto-Oncogene, GTPase), and among its related pathways/superpathways are NFAT and Cardiac Hypertrophy and p70S6K Signaling. Affiliated tissues include skin, brain and ovary, and related phenotypes are congenital giant melanocytic nevus and cutaneous melanoma

UniProtKB/Swiss-Prot : 75 Melanocytic nevus syndrome, congenital: A syndrome characterized by congenital pigmentary skin lesions which can occur at any site and can cover most of the body surface. These lesions may or may not be hairy. Congenital melanocytic nevi are associated with neuromelanosis (the presence of melanin-producing cells within the brain parenchyma or leptomeninges). Less commonly they are associated with malignant melanoma in childhood, both in the skin and the central nervous system. CMNS patients also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip. Nevus spilus: A congenital hyperpigmented patch, which progressively evolves, developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanoma. Spitz nevus: A benign melanocytic neoplasm composed of epithelioid or spindle cell melanocytes. Spitz nevi usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms.

Wikipedia : 76 The congenital melanocytic nevus is a type of melanocytic nevus (or mole) found in infants at birth.... more...

Related Diseases for Melanocytic Nevus Syndrome, Congenital

Diseases related to Melanocytic Nevus Syndrome, Congenital via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 67)
# Related Disease Score Top Affiliating Genes
1 giant congenital nevus 33.5 HRAS NRAS
2 nevus, epidermal 32.8 HRAS NRAS
3 lentigines 31.2 MC1R PRKAR1A
4 spitz nevus 12.6
5 lentigo maligna melanoma 12.4
6 molybdenum cofactor deficiency, complementation group c 11.8
7 phakomatosis pigmentokeratotica 11.6
8 phacomatosis pigmentokeratotica 11.6
9 phacomatosis pigmentovascularis 11.6
10 hyperekplexia 11.6
11 molybdenum cofactor deficiency 11.5
12 stiff-person syndrome 11.1
13 melanosis, neurocutaneous 11.1
14 spondylocostal dysostosis with anal atresia and urogenital anomalies 10.9
15 benign struma ovarii 10.7 HRAS NRAS
16 schimmelpenning-feuerstein-mims syndrome 10.7 HRAS NRAS
17 ovarian melanoma 10.7 HRAS NRAS
18 malignant conjunctival melanoma 10.7 HRAS NRAS
19 melanomatosis 10.6 HRAS NRAS
20 marcus gunn phenomenon 10.6 HRAS NRAS
21 malignant struma ovarii 10.6 HRAS NRAS
22 myelodysplastic myeloproliferative cancer 10.6 HRAS NRAS
23 meningeal melanomatosis 10.6 HRAS NRAS
24 acneiform dermatitis 10.5 HRAS NRAS
25 malignant spindle cell melanoma 10.5 NRAS TYR
26 epithelioid cell melanoma 10.4 PRKAR1A TYR
27 core binding factor acute myeloid leukemia 10.4 HRAS NRAS
28 liver angiosarcoma 10.3 HRAS NRAS
29 vulvar melanoma 10.3 HRAS NRAS TYR
30 malignant skin fibrous histiocytoma 10.3 HRAS NRAS TYR
31 malignant dermis tumor 10.3 HRAS NRAS TYR
32 central nervous system melanocytic neoplasm 10.3 HRAS NRAS TYR
33 congenital nystagmus 10.2 MC1R TYR
34 melanoma, uveal 10.2 MC1R NRAS TYR
35 diffuse meningeal melanocytosis 10.1 EDN1 TYR
36 congenital mesoblastic nephroma 10.1
37 acute contagious conjunctivitis 10.1 MC1R TYR
38 melanoma 10.0
39 leukemia, chronic myeloid 10.0 HRAS KITLG NRAS
40 melanoma, cutaneous malignant 1 10.0 HRAS MC1R NRAS STK11
41 lymphedema 9.9
42 cutaneous mastocytosis 9.9
43 dystonia 9.9
44 neurofibroma 9.9
45 integumentary system cancer 9.9 HRAS MC1R NRAS TYR
46 cell type cancer 9.9 HRAS MC1R NRAS TYR
47 appendix carcinoid tumor 9.8 MLH1 MSH2
48 adenosquamous colon carcinoma 9.8 MLH1 MSH2
49 sebaceous adenoma 9.8 MLH1 MSH2
50 lower lip cancer 9.8 MLH1 MSH2

Graphical network of the top 20 diseases related to Melanocytic Nevus Syndrome, Congenital:



Diseases related to Melanocytic Nevus Syndrome, Congenital

Symptoms & Phenotypes for Melanocytic Nevus Syndrome, Congenital

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Nose:
short nose
anteverted nares
broad nasal tip
narrow nasal ridge
small nose
more
Head And Neck Eyes:
periorbital fullness
apparent hypertelorism
eyebrow abnormalities

Skin Nails Hair Skin:
large nevus (greater than 10 cm)
multiple nevi (up to hundreds)
giant pigmented hairy nevus, often in lumbosacral distribution
hair may not be present on the nevus
nevus spilus
more
Head And Neck Face:
prominent forehead
full cheeks
long philtrum
round face
deep philtrum
more
Head And Neck Mouth:
open mouth
everted lower lip

Neoplasia:
susceptibility to malignant melanoma


Clinical features from OMIM:

137550

Human phenotypes related to Melanocytic Nevus Syndrome, Congenital:

59 32 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 congenital giant melanocytic nevus 59 32 Very frequent (99-80%) HP:0005600
2 cutaneous melanoma 59 32 Occasional (29-5%) HP:0012056
3 hydrocephalus 59 Occasional (29-5%)
4 pruritus 59 Occasional (29-5%)
5 abnormality of skin pigmentation 59 Very frequent (99-80%)
6 hypopigmented skin patches 59 Occasional (29-5%)
7 seizures 59 Occasional (29-5%)
8 subcutaneous nodule 59 Occasional (29-5%)
9 generalized hirsutism 59 Frequent (79-30%)
10 neoplasm 59 Frequent (79-30%)
11 rhabdomyosarcoma 59 Occasional (29-5%)
12 nevus 59 Very frequent (99-80%)
13 neoplasm of the skin 59 Occasional (29-5%)
14 sarcoma 59 Occasional (29-5%)
15 open mouth 32 HP:0000194
16 everted lower lip vermilion 32 HP:0000232
17 full cheeks 32 HP:0000293
18 round face 32 HP:0000311
19 broad forehead 32 HP:0000337
20 long philtrum 32 HP:0000343
21 narrow nasal ridge 32 HP:0000418
22 broad nasal tip 32 HP:0000455
23 periorbital fullness 32 HP:0000629
24 deep philtrum 32 HP:0002002
25 short nose 32 HP:0003196
26 prominence of the premaxilla 32 HP:0010759
27 prominent forehead 32 HP:0011220

MGI Mouse Phenotypes related to Melanocytic Nevus Syndrome, Congenital:

46 (show all 14)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.13 KITLG MC1R MLH1 MSH2 NRAS PRKAR1A
2 craniofacial MP:0005382 10.11 KITLG MC1R NRAS PRKAR1A STK11 TYR
3 digestive/alimentary MP:0005381 10.1 EDN1 HRAS KITLG MLH1 MSH2 NRAS
4 cardiovascular system MP:0005385 10.08 EDN1 HRAS KITLG NRAS PRKAR1A STK11
5 endocrine/exocrine gland MP:0005379 10.06 EDN1 HRAS KITLG MLH1 NRAS PRKAR1A
6 homeostasis/metabolism MP:0005376 10.06 HRAS KITLG MLH1 MSH2 NRAS PRKAR1A
7 growth/size/body region MP:0005378 10.03 EDN1 HRAS KITLG MC1R NRAS PRKAR1A
8 integument MP:0010771 10.02 HRAS KITLG MC1R MLH1 MSH2 NRAS
9 mortality/aging MP:0010768 9.97 EDN1 HRAS KITLG MLH1 MSH2 NRAS
10 embryo MP:0005380 9.95 EDN1 KITLG NRAS PRKAR1A STK11 TYR
11 neoplasm MP:0002006 9.91 HRAS KITLG MC1R MLH1 MSH2 NRAS
12 normal MP:0002873 9.63 TYR EDN1 HRAS NRAS PRKAR1A STK11
13 pigmentation MP:0001186 9.35 KITLG MC1R NRAS PRKAR1A TYR
14 vision/eye MP:0005391 9.1 PRKAR1A STK11 TYR KITLG MLH1 NRAS

Drugs & Therapeutics for Melanocytic Nevus Syndrome, Congenital

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Efficacy and Safety of a Nanofat-seeded Biological Scaffold in Healing Lower Limb Surgical Defects Not yet recruiting NCT03548610 Phase 2, Phase 3
2 Autologous Engineered Skin Substitutes for Closure of Skin Wounds Terminated NCT00591513 Phase 2, Phase 3
3 Natural History Study of Moles and Suspicious Melanoma Completed NCT00288938

Search NIH Clinical Center for Melanocytic Nevus Syndrome, Congenital

Cochrane evidence based reviews: lentigo

Genetic Tests for Melanocytic Nevus Syndrome, Congenital

Anatomical Context for Melanocytic Nevus Syndrome, Congenital

MalaCards organs/tissues related to Melanocytic Nevus Syndrome, Congenital:

41
Skin, Brain, Ovary

Publications for Melanocytic Nevus Syndrome, Congenital

Articles related to Melanocytic Nevus Syndrome, Congenital:

# Title Authors Year
1
Pigmented mole in a dermoid cyst of ovary: report of a case. ( 13467299 )
1957

Variations for Melanocytic Nevus Syndrome, Congenital

UniProtKB/Swiss-Prot genetic disease variations for Melanocytic Nevus Syndrome, Congenital:

75
# Symbol AA change Variation ID SNP ID
1 NRAS p.Gly13Arg VAR_006845 rs121434595
2 NRAS p.Gln61Lys VAR_006846 rs121913254
3 NRAS p.Gln61Arg VAR_006847 rs11554290

ClinVar genetic disease variations for Melanocytic Nevus Syndrome, Congenital:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NRAS NM_002524.4(NRAS): c.37G> C (p.Gly13Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121434595 GRCh37 Chromosome 1, 115258745: 115258745
2 NRAS NM_002524.4(NRAS): c.37G> C (p.Gly13Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121434595 GRCh38 Chromosome 1, 114716124: 114716124
3 NRAS NM_002524.4(NRAS): c.182A> G (p.Gln61Arg) single nucleotide variant Pathogenic rs11554290 GRCh37 Chromosome 1, 115256529: 115256529
4 NRAS NM_002524.4(NRAS): c.182A> G (p.Gln61Arg) single nucleotide variant Pathogenic rs11554290 GRCh38 Chromosome 1, 114713908: 114713908
5 NRAS NM_002524.4(NRAS): c.181C> A (p.Gln61Lys) single nucleotide variant Pathogenic/Likely pathogenic,drug response rs121913254 GRCh37 Chromosome 1, 115256530: 115256530
6 NRAS NM_002524.4(NRAS): c.181C> A (p.Gln61Lys) single nucleotide variant Pathogenic/Likely pathogenic,drug response rs121913254 GRCh38 Chromosome 1, 114713909: 114713909
7 NRAS NM_002524.4(NRAS): c.181C> A (p.Gln61Lys) single nucleotide variant Pathogenic/Likely pathogenic,drug response rs121913254 NCBI36 Chromosome 1, 115058053: 115058053
8 46;X;inv(X)(q26q28)dn inversion Uncertain significance

Expression for Melanocytic Nevus Syndrome, Congenital

Search GEO for disease gene expression data for Melanocytic Nevus Syndrome, Congenital.

Pathways for Melanocytic Nevus Syndrome, Congenital

Pathways related to Melanocytic Nevus Syndrome, Congenital according to GeneCards Suite gene sharing:

(show all 24)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.65 EDN1 HRAS NRAS PRKAR1A
2
Show member pathways
12.65 HRAS KITLG NRAS PRKAR1A STK11
3
Show member pathways
12.61 HRAS MLH1 MSH2 NRAS
4
Show member pathways
12.56 EDN1 HRAS KITLG NRAS PRKAR1A
5 12.38 HRAS KITLG MLH1 MSH2 NRAS
6
Show member pathways
12.29 EDN1 HRAS KITLG MC1R NRAS TYR
7 11.94 MLH1 MSH2 PRKAR1A
8
Show member pathways
11.88 HRAS NRAS PRKAR1A
9
Show member pathways
11.87 HRAS NRAS STK11
10
Show member pathways
11.79 HRAS NRAS STK11
11 11.74 HRAS NRAS STK11
12 11.49 EDN1 HRAS NRAS
13 11.15 HRAS NRAS
14
Show member pathways
11.08 EDN1 HRAS
15 11.08 HRAS NRAS
16 11.07 HRAS NRAS
17
Show member pathways
11.05 HRAS NRAS
18 11.04 MLH1 MSH2
19 10.94 KITLG MC1R PRKAR1A
20 10.92 HRAS NRAS
21 10.88 HRAS NRAS
22 10.8 HRAS NRAS
23 10.55 HRAS NRAS
24
Show member pathways
10.21 EDN1 HRAS NRAS

GO Terms for Melanocytic Nevus Syndrome, Congenital

Cellular components related to Melanocytic Nevus Syndrome, Congenital according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mismatch repair complex GO:0032300 8.62 MLH1 MSH2

Biological processes related to Melanocytic Nevus Syndrome, Congenital according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell cycle arrest GO:0007050 9.61 HRAS MSH2 STK11
2 mismatch repair GO:0006298 9.48 MLH1 MSH2
3 positive regulation of Ras protein signal transduction GO:0046579 9.46 HRAS KITLG
4 positive regulation of MAP kinase activity GO:0043406 9.43 EDN1 HRAS KITLG
5 somatic hypermutation of immunoglobulin genes GO:0016446 9.4 MLH1 MSH2
6 isotype switching GO:0045190 9.37 MLH1 MSH2
7 positive regulation of isotype switching to IgG isotypes GO:0048304 9.32 MLH1 MSH2
8 positive regulation of isotype switching to IgA isotypes GO:0048298 9.16 MLH1 MSH2
9 somatic recombination of immunoglobulin gene segments GO:0016447 8.96 MLH1 MSH2
10 somatic recombination of immunoglobulin genes involved in immune response GO:0002204 8.62 MLH1 MSH2

Molecular functions related to Melanocytic Nevus Syndrome, Congenital according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mismatched DNA binding GO:0030983 8.96 MLH1 MSH2
2 guanine/thymine mispair binding GO:0032137 8.62 MLH1 MSH2

Sources for Melanocytic Nevus Syndrome, Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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