Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurocutaneous melanosis is an extremely rare disease characterized by large or multiple congenital melanocytic nevi and benign or malignant proliferation of melanocytes in the central nervous system. Neurological manifestations usually develop during the first three years of life and the prognosis of patients with NCM who manifest neurological symptoms is very poor. Here we describe a 9-year-old girl who manifested neurological symptoms caused by communicating hydrocephalus and died of proliferation of melanocytes in the central nervous system 11 months after the initial symptoms. Serum and cerebrospinal fluid 5-S-CD levels could be a useful marker of disease progression, even in patients with NCM without apparent malignant findings at initial biopsy.
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PMID:Rapidly progressive and fatal neurocutaneous melanosis presenting as recurrent headache. 2367 65

Neurocutaneous melanosis (NCM; MIM # 249400; ORPHA: 2481], first reported by the Bohemian pathologist Rokitansky in 1861, and now more precisely defined as neurocutaneous melanocytosis, is a rare, congenital syndrome characterised by the association of (1) congenital melanocytic nevi (CMN) of the skin with overlying hypertrichosis, presenting as (a) large (LCMN) or giant and/or multiple (MCMN) melanocytic lesions (or both; sometimes associated with smaller "satellite" nevi) or (b) as proliferative melanocytic nodules; and (2) melanocytosis (with infiltration) of the brain parenchyma and/or leptomeninges. CMN of the skin and leptomeningeal/nervous system infiltration are usually benign, more rarely may progress to melanoma or non-malignant melanosis of the brain. Approximately 12% of individuals with LCMN will develop NCM: wide extension and/or dorsal axial distribution of LCMN increases the risk of NCM. The CMN are recognised at birth and are distributed over the skin according to 6 or more patterns (6B patterns) in line with the archetypical patterns of distribution of mosaic skin disorders. Neurological manifestations can appear acutely in infancy, or more frequently later in childhood or adult life, and include signs/symptoms of intracranial hypertension, seizures/epilepsy, cranial nerve palsies, motor/sensory deficits, cognitive/behavioural abnormalities, sleep cycle anomalies, and eventually neurological deterioration. NMC patients may be symptomatic or asymptomatic, with or without evidence of the typical nervous system changes at MRI. Associated brain and spinal cord malformations include the Dandy-Walker malformation (DWM) complex, hemimegalencephaly, cortical dysplasia, arachnoid cysts, Chiari I and II malformations, syringomyelia, meningoceles, occult spinal dysraphism, and CNS lipoma/lipomatosis. There is no systemic involvement, or only rarely. Pathogenically, single postzygotic mutations in the NRAS (neuroblastoma RAS viral oncogene homologue; MIM # 164790; at 1p13.2) proto-oncogene explain the occurrence of single/multiple CMNs and melanocytic and non-melanocytic nervous system lesions in NCM: these disrupt the RAS/ERK/mTOR/PI3K/akt pathways. Diagnostic/surveillance work-ups require physical examination, ophthalmoscopy, brain/spinal cord magnetic resonance imaging (MRI) and angiography (MRA), positron emission tomography (PET), and video-EEG and IQ testing. Treatment strategies include laser therapy, chemical peeling, dermabrasion, and surgical removal/grafting for CMNs and shunt surgery and surgical removal/chemo/radiotherapy for CNS lesions. Biologically targeted therapies tailored (a) BRAF/MEK in NCM mice (MEK162) and GCMN (trametinib); (b) PI3K/mTOR (omipalisib/GSK2126458) in NMC cells; (c) RAS/MEK (vemurafenib and trametinib) in LCMNs cells; or created experimental NMC cells (YP-MEL).
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PMID:Neurocutaneous melanocytosis (melanosis). 3304 48