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Neurocutaneous melanocytosis(NCMS)

MedGen UID:
154259
Concept ID:
C0544862
Congenital Abnormality
Synonyms: NCMS; Neurocutaneous melanosis; Neurocutaneous melanosis syndrome; NEUROCUTANEOUS MELANOSIS, SOMATIC; NEUROMELANOSIS
SNOMED CT: Neurocutaneous melanosis (1141661004)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): NRAS (1p13.2)
 
Monarch Initiative: MONDO:0009578
OMIM®: 249400
Orphanet: ORPHA2481

Definition

Neurocutaneous melanosis, or neuromelanosis, is characterized by the presence of melanin-producing cells within the brain parenchyma or leptomeninges, which may lead to clinically apparent neurologic signs and symptoms, such as seizures. Other neurologic abnormalities, including hydrocephalus, arachnoid cysts, tumors, and syringomyelia, may also occur. The disorder is a rare but severe manifestation of congenital melanocytic nevus syndrome (CMNS; 137550). Some patients with neurocutaneous melanosis or CMNS may develop malignant melanoma. The incidence of neurologic involvement, development of malignant melanoma, and death is significantly associated with the projected adult size of the largest congenital melanocytic nevus, particularly those greater than 40 cm (summary by Kinsler et al., 2008; Kinsler et al., 2013). [from OMIM]

Clinical features

From HPO
Melanoma
MedGen UID:
9944
Concept ID:
C0025202
Neoplastic Process
Melanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults.\n\nA large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed.\n\nMelanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white.\n\nMost melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize).
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Meningioma
MedGen UID:
7532
Concept ID:
C0025286
Neoplastic Process
The presence of a meningioma, i.e., a benign tumor originating from the dura mater or arachnoid mater.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Syringomyelia
MedGen UID:
21449
Concept ID:
C0039144
Disease or Syndrome
Dilated, glial-lined cavity in spinal cord. This cavity does not communicate with the central canal, and usually is between the dorsal columns unilaterally or bilaterally along the side of the cord.
Arachnoid cyst
MedGen UID:
86860
Concept ID:
C0078981
Disease or Syndrome
An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid.
Cranial nerve paralysis
MedGen UID:
57717
Concept ID:
C0151311
Disease or Syndrome
Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.
Choroid plexus papilloma
MedGen UID:
64439
Concept ID:
C0205770
Neoplastic Process
Choroid plexus tumors are of neuroectodermal origin and range from benign choroid plexus papillomas (CPPs) to malignant choroid carcinomas (CPCs). These rare tumors generally occur in childhood, but have also been reported in adults. Patients typically present with signs and symptoms of increased intracranial pressure including headache, hydrocephalus, papilledema, nausea, vomiting, cranial nerve deficits, gait impairment, and seizures (summary by Safaee et al., 2013).
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Dandy-Walker malformation
MedGen UID:
419183
Concept ID:
C2931867
Congenital Abnormality
A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal.
Numerous congenital melanocytic nevi
MedGen UID:
812745
Concept ID:
C3806415
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeurocutaneous melanocytosis
Follow this link to review classifications for Neurocutaneous melanocytosis in Orphanet.

Professional guidelines

PubMed

Elisabeth Wramp M, Langenbruch A, Augustin M, Zillikens D, Krengel S
J Dtsch Dermatol Ges 2017 Feb;15(2):159-167. doi: 10.1111/ddg.12835. PMID: 28214318
Marghoob AA, Borrego JP, Halpern AC
Semin Cutan Med Surg 2007 Dec;26(4):231-40. doi: 10.1016/j.sder.2008.03.007. PMID: 18395671
Marghoob AA, Borrego JP, Halpern AC
Semin Cutan Med Surg 2003 Mar;22(1):21-32. doi: 10.1053/sder.2003.50002. PMID: 12773011

Recent clinical studies

Etiology

Farabi B, Akay BN, Goldust M, Wollina U, Atak MF, Rao B
Australas J Dermatol 2021 May;62(2):e178-e191. Epub 2021 Feb 16 doi: 10.1111/ajd.13535. PMID: 33591589
Mitre V, Heym K, Clark GD, Venkatramani R
J Pediatr Hematol Oncol 2021 Mar 1;43(2):e195-e197. doi: 10.1097/MPH.0000000000001680. PMID: 31764519
Ruggieri M, Polizzi A, Catanzaro S, Bianco ML, Praticò AD, Di Rocco C
Childs Nerv Syst 2020 Oct;36(10):2571-2596. Epub 2020 Oct 13 doi: 10.1007/s00381-020-04770-9. PMID: 33048248
Moustafa D, Blundell AR, Hawryluk EB
Curr Opin Pediatr 2020 Aug;32(4):491-497. doi: 10.1097/MOP.0000000000000924. PMID: 32692047
Chernoff KA, Schaffer JV
Clin Dermatol 2016 Mar-Apr;34(2):183-204. Epub 2015 Nov 22 doi: 10.1016/j.clindermatol.2015.11.003. PMID: 26903185

Diagnosis

Farabi B, Akay BN, Goldust M, Wollina U, Atak MF, Rao B
Australas J Dermatol 2021 May;62(2):e178-e191. Epub 2021 Feb 16 doi: 10.1111/ajd.13535. PMID: 33591589
Ruggieri M, Polizzi A, Catanzaro S, Bianco ML, Praticò AD, Di Rocco C
Childs Nerv Syst 2020 Oct;36(10):2571-2596. Epub 2020 Oct 13 doi: 10.1007/s00381-020-04770-9. PMID: 33048248
Constantini S, Schuhmann MU
Childs Nerv Syst 2020 Oct;36(10):2227-2228. Epub 2020 Jul 13 doi: 10.1007/s00381-020-04794-1. PMID: 32661640Free PMC Article
Chernoff KA, Schaffer JV
Clin Dermatol 2016 Mar-Apr;34(2):183-204. Epub 2015 Nov 22 doi: 10.1016/j.clindermatol.2015.11.003. PMID: 26903185
Flores-Sarnat L
Handb Clin Neurol 2013;111:369-88. doi: 10.1016/B978-0-444-52891-9.00042-7. PMID: 23622187

Therapy

Mitre V, Heym K, Clark GD, Venkatramani R
J Pediatr Hematol Oncol 2021 Mar 1;43(2):e195-e197. doi: 10.1097/MPH.0000000000001680. PMID: 31764519
Mir A, Agim NG, Kane AA, Josephs SC, Park JY, Ludwig K
Pediatrics 2019 Mar;143(3) doi: 10.1542/peds.2018-2469. PMID: 30792255
Ruan Y, Kovalchuk A, Jayanthan A, Lun X, Nagashima Y, Kovalchuk O, Wright JR Jr, Pinto A, Kirton A, Anderson R, Narendran A
Neuro Oncol 2015 Jun;17(6):822-31. Epub 2014 Nov 12 doi: 10.1093/neuonc/nou310. PMID: 25395461Free PMC Article
Küsters-Vandevelde HV, Willemsen AE, Groenen PJ, Küsters B, Lammens M, Wesseling P, Djafarihamedani M, Rijntjes J, Delye H, Willemsen MA, van Herpen CM, Blokx WA
Acta Neuropathol Commun 2014 Apr 8;2:41. doi: 10.1186/2051-5960-2-41. PMID: 24713450Free PMC Article
Cajaiba MM, Benjamin D, Halaban R, Reyes-Múgica M
Am J Surg Pathol 2008 Jan;32(1):156-61. doi: 10.1097/PAS.0b013e3181238cd2. PMID: 18162783

Prognosis

Ruth J
Semin Pediatr Neurol 2024 Oct;51:101153. Epub 2024 Sep 13 doi: 10.1016/j.spen.2024.101153. PMID: 39389659
Rahman RK, Majmundar N, Ghani H, San A, Koirala M, Gajjar AA, Pappert A, Mazzola CA
Neurosurg Focus 2022 May;52(5):E8. doi: 10.3171/2022.2.FOCUS21791. PMID: 35535823
Mitre V, Heym K, Clark GD, Venkatramani R
J Pediatr Hematol Oncol 2021 Mar 1;43(2):e195-e197. doi: 10.1097/MPH.0000000000001680. PMID: 31764519
Moustafa D, Blundell AR, Hawryluk EB
Curr Opin Pediatr 2020 Aug;32(4):491-497. doi: 10.1097/MOP.0000000000000924. PMID: 32692047
Magaña M, Sánchez-Romero E, Magaña P, Beck-Magaña A, Magaña-Lozano M
Am J Dermatopathol 2015 Jan;37(1):31-7. doi: 10.1097/DAD.0000000000000183. PMID: 25140664

Clinical prediction guides

Ruth J
Semin Pediatr Neurol 2024 Oct;51:101153. Epub 2024 Sep 13 doi: 10.1016/j.spen.2024.101153. PMID: 39389659
Rahman RK, Majmundar N, Ghani H, San A, Koirala M, Gajjar AA, Pappert A, Mazzola CA
Neurosurg Focus 2022 May;52(5):E8. doi: 10.3171/2022.2.FOCUS21791. PMID: 35535823
Moustafa D, Blundell AR, Hawryluk EB
Curr Opin Pediatr 2020 Aug;32(4):491-497. doi: 10.1097/MOP.0000000000000924. PMID: 32692047
Magaña M, Sánchez-Romero E, Magaña P, Beck-Magaña A, Magaña-Lozano M
Am J Dermatopathol 2015 Jan;37(1):31-7. doi: 10.1097/DAD.0000000000000183. PMID: 25140664
Slutsky JB, Barr JM, Femia AN, Marghoob AA
Semin Cutan Med Surg 2010 Jun;29(2):79-84. doi: 10.1016/j.sder.2010.04.007. PMID: 20579596

Recent systematic reviews

Rahman RK, Majmundar N, Ghani H, San A, Koirala M, Gajjar AA, Pappert A, Mazzola CA
Neurosurg Focus 2022 May;52(5):E8. doi: 10.3171/2022.2.FOCUS21791. PMID: 35535823

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