CMNS
MCID: MLN065
MIFTS: 54

Melanocytic Nevus Syndrome, Congenital (CMNS)

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases, Smell/Taste 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


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 nodular malignant melanoma. An important gene associated with Melanocytic Nevus Syndrome, Congenital is NRAS (NRAS Proto-Oncogene, GTPase), and among its related pathways/superpathways are TCR Signaling (Qiagen) and p70S6K Signaling. The drugs Lidocaine and Anesthetics have been mentioned in the context of this disorder. Affiliated tissues include skin, brain and kidney, and related phenotypes are hydrocephalus and seizures

Genetics Home Reference : 25 Giant congenital melanocytic nevus is a skin condition characterized by an abnormally dark, noncancerous skin patch (nevus) that is composed of pigment-producing cells called melanocytes. It is present from birth (congenital) or is noticeable soon after birth. The nevus may be small in infants, but it will usually grow at the same rate the body grows and will eventually be at least 40 cm (15.75 inches) across. The nevus can appear anywhere on the body, but it is more often found on the trunk or limbs. The color ranges from tan to black and can become darker or lighter over time. The surface of a nevus can be flat, rough, raised, thickened, or bumpy; the surface can vary in different regions of the nevus, and it can change over time. The skin of the nevus is often dry and prone to irritation and itching (dermatitis). Excessive hair growth (hypertrichosis) can occur within the nevus. There is often less fat tissue under the skin of the nevus; the skin may appear thinner there than over other areas of the body.

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 175)
# Related Disease Score Top Affiliating Genes
1 giant congenital nevus 32.8 NRAS HRAS
2 nodular malignant melanoma 30.5 NRAS HRAS
3 lentigines 30.3 PRKAR1A MC1R
4 vitiligo-associated multiple autoimmune disease susceptibility 1 30.2 TYR MC1R KITLG
5 spitz nevus 12.8
6 lentigo maligna melanoma 12.5
7 molybdenum cofactor deficiency, complementation group c 11.9
8 phacomatosis pigmentovascularis 11.8
9 molybdenum cofactor deficiency 11.7
10 hyperekplexia 11.7
11 nevus, epidermal 11.5
12 stiff-person syndrome 11.3
13 melanosis, neurocutaneous 11.2
14 becker nevus syndrome 11.2
15 molybdenum cofactor deficiency, complementation group a 11.1
16 spastic paraplegia 24, autosomal recessive 11.1
17 leber congenital amaurosis 13 11.1
18 retinal dystrophy, juvenile cataracts, and short stature syndrome 11.1
19 glycosylphosphatidylinositol biosynthesis defect 17 11.1
20 mediastinal cancer 11.1
21 geniculate herpes zoster 11.1
22 acute monoblastic leukemia 11.1
23 spondylocostal dysostosis with anal atresia and urogenital anomalies 11.1
24 mosaic trisomy 22 11.1
25 retinitis pigmentosa 11.0
26 leber congenital amaurosis 11.0
27 keratosis 10.4
28 congenital mesoblastic nephroma 10.3
29 melanoma 10.3
30 neurofibroma 10.3
31 basal cell carcinoma 1 10.3
32 basal cell carcinoma 10.3
33 actinic keratosis 10.3
34 hemangioma 10.2
35 tièche-jadassohn nevus 10.2
36 benign struma ovarii 10.2 NRAS HRAS
37 schimmelpenning-feuerstein-mims syndrome 10.2 NRAS HRAS
38 ovarian melanoma 10.2 NRAS HRAS
39 melanomatosis 10.2 NRAS HRAS
40 malignant conjunctival melanoma 10.2 NRAS HRAS
41 marcus gunn phenomenon 10.2 NRAS HRAS
42 malignant struma ovarii 10.2 NRAS HRAS
43 rhabdomyosarcoma 10.2
44 fetal adenoma 10.2 NRAS HRAS
45 meningeal melanomatosis 10.2 NRAS HRAS
46 myelodysplastic myeloproliferative cancer 10.2 NRAS HRAS
47 acneiform dermatitis 10.2 NRAS HRAS
48 malignant spindle cell melanoma 10.2 TYR NRAS
49 dermatitis 10.2
50 granulomatous dermatitis 10.2

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 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000238
2 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
3 subcutaneous nodule 59 32 occasional (7.5%) Occasional (29-5%) HP:0001482
4 pruritus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000989
5 generalized hirsutism 59 32 frequent (33%) Frequent (79-30%) HP:0002230
6 hypopigmented skin patches 59 32 occasional (7.5%) Occasional (29-5%) HP:0001053
7 rhabdomyosarcoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0002859
8 congenital giant melanocytic nevus 59 32 hallmark (90%) Very frequent (99-80%) HP:0005600
9 cutaneous melanoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0012056
10 hypertelorism 32 HP:0000316
11 short nose 32 HP:0003196
12 prominent forehead 32 HP:0011220
13 full cheeks 32 HP:0000293
14 long philtrum 32 HP:0000343
15 neoplasm 59 Frequent (79-30%)
16 periorbital fullness 32 HP:0000629
17 everted lower lip vermilion 32 HP:0000232
18 nevus 59 Very frequent (99-80%)
19 broad forehead 32 HP:0000337
20 sarcoma 59 Occasional (29-5%)
21 open mouth 32 HP:0000194
22 round face 32 HP:0000311
23 broad nasal tip 32 HP:0000455
24 deep philtrum 32 HP:0002002
25 neoplasm of the skin 59 Occasional (29-5%)
26 abnormality of skin pigmentation 59 Very frequent (99-80%)
27 narrow nasal ridge 32 HP:0000418
28 prominence of the premaxilla 32 HP:0010759

MGI Mouse Phenotypes related to Melanocytic Nevus Syndrome, Congenital:

46 (show all 15)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.14 KITLG MC1R MLH1 MSH2 NRAS PRKAR1A
2 craniofacial MP:0005382 10.13 EDN1 HRAS KITLG MC1R NRAS PRKAR1A
3 digestive/alimentary MP:0005381 10.11 EDN1 HRAS KITLG MLH1 MSH2 NRAS
4 cardiovascular system MP:0005385 10.09 EDN1 HRAS KITLG NRAS PRKAR1A STK11
5 homeostasis/metabolism MP:0005376 10.09 EDN1 HRAS KITLG MLH1 MSH2 NRAS
6 endocrine/exocrine gland MP:0005379 10.08 EDN1 HRAS KITLG MLH1 NRAS PRKAR1A
7 growth/size/body region MP:0005378 10.06 EDN1 HRAS KITLG MC1R NRAS PRKAR1A
8 integument MP:0010771 10.02 HRAS KITLG MC1R MLH1 MSH2 NRAS
9 immune system MP:0005387 10.01 KITLG MC1R MLH1 MSH2 NRAS PRKAR1A
10 embryo MP:0005380 9.97 EDN1 KITLG NRAS PRKAR1A STK11 TYR
11 mortality/aging MP:0010768 9.97 EDN1 HRAS KITLG MLH1 MSH2 NRAS
12 neoplasm MP:0002006 9.91 HRAS KITLG MC1R MLH1 MSH2 NRAS
13 normal MP:0002873 9.63 EDN1 HRAS NRAS PRKAR1A STK11 TYR
14 pigmentation MP:0001186 9.35 KITLG MC1R NRAS PRKAR1A TYR
15 vision/eye MP:0005391 9.1 KITLG MLH1 NRAS PRKAR1A STK11 TYR

Drugs & Therapeutics for Melanocytic Nevus Syndrome, Congenital

Drugs for Melanocytic Nevus Syndrome, Congenital (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lidocaine Approved, Vet_approved Phase 2, Phase 3 137-58-6 3676
2 Anesthetics Phase 2, Phase 3
3 Sunscreening Agents Phase 2, Phase 3
4 Calamus Phase 2, Phase 3

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 Recruiting NCT03548610 Phase 2, Phase 3
2 Autologous Engineered Skin Substitutes for Closure of Skin Wounds Terminated NCT00591513 Phase 2, Phase 3

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, Kidney, Colon, Smooth Muscle, Myeloid, Small Intestine

Publications for Melanocytic Nevus Syndrome, Congenital

Articles related to Melanocytic Nevus Syndrome, Congenital:

# Title Authors Year
1
"Giant pigmented hairy nevus in von-Recklinghausen's disease". ( 3108231 )
1986
2
Inheritance of giant pigmented hairy nevus of the scalp. ( 7258230 )
1981
3
Giant pigmented hairy nevus in two siblings. ( 4426633 )
1974
4
Giant pigmented hairy nevus. ( 5975780 )
1966

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 Uncertain significance rs121913254 GRCh37 Chromosome 1, 115256530: 115256530
6 NRAS NM_002524.4(NRAS): c.181C> A (p.Gln61Lys) single nucleotide variant Uncertain significance rs121913254 GRCh38 Chromosome 1, 114713909: 114713909
7 NRAS NM_002524.4(NRAS): c.181C> A (p.Gln61Lys) single nucleotide variant Uncertain significance rs121913254 NCBI36 Chromosome 1, 115058053: 115058053

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 27)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.71 HRAS MLH1 MSH2 NRAS
2
Show member pathways
12.71 HRAS KITLG NRAS PRKAR1A STK11
3
Show member pathways
12.63 EDN1 HRAS NRAS PRKAR1A
4
Show member pathways
12.63 HRAS MLH1 MSH2 NRAS
5
Show member pathways
12.56 EDN1 HRAS KITLG NRAS PRKAR1A
6 12.44 HRAS KITLG MLH1 MSH2 NRAS
7 11.96 MLH1 MSH2 PRKAR1A
8
Show member pathways
11.89 HRAS NRAS PRKAR1A
9
Show member pathways
11.88 HRAS NRAS STK11
10
Show member pathways
11.83 HRAS NRAS STK11
11 11.78 HRAS NRAS STK11
12 11.63 EDN1 HRAS NRAS
13
Show member pathways
11.51 EDN1 HRAS KITLG MC1R NRAS TYR
14 11.36 HRAS KITLG NRAS PRKAR1A
15 11.16 HRAS NRAS
16 11.16 HRAS MLH1 MSH2 NRAS
17
Show member pathways
11.1 EDN1 HRAS
18 11.09 HRAS NRAS
19 11.09 HRAS NRAS
20
Show member pathways
11.07 HRAS NRAS
21 11.06 MLH1 MSH2
22 10.94 HRAS NRAS
23 10.94 KITLG MC1R PRKAR1A
24 10.9 HRAS NRAS
25 10.85 HRAS NRAS
26 10.59 HRAS NRAS
27
Show member pathways
10.55 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:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 MAPK cascade GO:0000165 9.69 HRAS KITLG NRAS
2 cell cycle arrest GO:0007050 9.63 HRAS MSH2 STK11
3 mismatch repair GO:0006298 9.49 MLH1 MSH2
4 positive regulation of Ras protein signal transduction GO:0046579 9.48 HRAS KITLG
5 somatic hypermutation of immunoglobulin genes GO:0016446 9.43 MLH1 MSH2
6 positive regulation of MAP kinase activity GO:0043406 9.43 EDN1 HRAS KITLG
7 isotype switching GO:0045190 9.4 MLH1 MSH2
8 melanin biosynthetic process GO:0042438 9.37 MC1R TYR
9 positive regulation of isotype switching to IgG isotypes GO:0048304 9.32 MLH1 MSH2
10 positive regulation of isotype switching to IgA isotypes GO:0048298 9.16 MLH1 MSH2
11 somatic recombination of immunoglobulin gene segments GO:0016447 8.96 MLH1 MSH2
12 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
Content
Loading form....