Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?

Schepper, Sofie De; Boucneau, Joachim; Haeghen, Yves Vander; Messiaen, Ludwine; Naeyaert, Jean‐Marie; Lambert, Jo

doi:10.1007/s00403-006-0644-6

Cited by 55 publications

(41 citation statements)

References 53 publications

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“…SCF is a growth factor affecting growth, survival, cohesion and migration into tissue of melanocytes and mast cells, and it is also important in UVB-induced pigmentation [15]. Additional studies have highlighted higher levels of circulating SCF in serum of NF1 patients and an increased number of fibroblasts in NF1 CLS compared to NF1 and non-NF1 patients’ normal skin [16].…”

Section: Discussionmentioning

confidence: 99%

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Evolving Pattern with Age of Cutaneous Signs in Neurofibromatosis Type 1: A Cross-Sectional Study of 728 Patients

Duong

Bastuji‐Garin²,

Valeyrie‐Allanore

et al. 2011

Dermatology

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Background: Neurofibromatosis type 1 is fully penetrant by the age of 8 years, and 3 criteria of diagnosis are dermatological: café-au-lait spots (CLS), intertriginous freckling and neurofibromas (NF). Objectives: The aim of our study was to determine the evolving pattern of cutaneous manifestations during adulthood. Methods: Phenotypic data of patients seen in our center between March 2003 and December 2009 were studied. Patients were classified in 10-year groups. Following clinical characteristics, the number of CLS and the number of cutaneous and subcutaneous NF were compared according to age. Results: 728 subjects, 404 females and 324 males (mean age of 32.4 years, range 6–80 years) were studied. Four hundred eighty-nine patients were over 20 years old (67%). The number of CLS (small or large) was significantly decreased with age while the number of cutaneous and subcutaneous NF was strongly increased (p < 0.001). Conclusions: The decrease in CLS with age has not been previously reported while an increase in the number of NF is well described during puberty and pregnancy and with age.

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Section: Discussionmentioning

confidence: 99%

“…Histological comparison between NF1 CLS and non-NF1 individual CLS showed an increased number of melanocytes with normal amounts of tyrosinase activity and a larger amount of melanin in NF1 CLS [15]. NF1 CLS and normal skin had also an increased secretion of stem cell factor (SCF) in comparison to non-NF1 CLS and normal skin.…”

Section: Discussionmentioning

confidence: 99%

Evolving Pattern with Age of Cutaneous Signs in Neurofibromatosis Type 1: A Cross-Sectional Study of 728 Patients

Duong

Bastuji‐Garin²,

Valeyrie‐Allanore

et al. 2011

Dermatology

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“…They can be present at birth, although they usually become detectable during early childhood, growing proportionately to body growth, but they have no tendency toward malignancy. De Schepper et al 72,73 showed that melanocytes cultured from café-au-lait macules of patients with NF1 carry a somatic or second-hit mutation in the NF1 gene, suggesting that the melanocyte is the primary pathogenic cell in these pigmented lesions. This notion increases the understanding of the pathoetiology of these lesions.…”

Section: Nf1 Lesions Caused By Loh or Somatic Second-hit Mutationsmentioning

confidence: 99%

The Pathoetiology of Neurofibromatosis 1

Jouhilahti

Peltonen

Heape

et al. 2011

The American Journal of Pathology

158

150

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Although a mutation in the NF1 gene is the only factor required to initiate the neurocutaneous-skeletal neurofibromatosis 1 (NF1) syndrome, the pathoetiology of the multiple manifestations of this disease in different organ systems seems increasingly complex. The wide spectrum of different clinical phenotypes and their development, severity, and prognosis seem to result from the cross talk between numerous cell types, cell signaling networks, and cell-extracellular matrix interactions. The bi-allelic inactivation of the NF1 gene through a "second hit" seems to be of crucial importance to the development of certain manifestations, such as neurofibromas, café-au-lait macules, and glomus tumors. In each case, the second hit involves only one cell type, which is subsequently clonally expanded in a discrete lesion. Neurofibromas, which are emphasized in this review, and cutaneous neurofibromas in particular, are known to contain a subpopulation of NF1-diploinsufficient Schwann cells and a variety of NF1-haploinsufficient cell types. A recent study identified a multipotent precursor cell population with an NF1 ؉/؊ genotype that resides in human cutaneous neurofibromas and that has been suggested to play a role in their pathogenesis. café-au-lait macules and multiple benign cutaneous neurofibromas, which, typically, are detectable in adulthood by simple visual inspection.NF1 can affect nearly every organ system, and the complications vary between individuals, even within a single family. The clinical diagnosis is based on the presence of two or more of the following findings: six or more café-au-lait macules with diameters Ͼ5 mm in prepubertal patients and Ͼ15 mm in postpubertal patients; two or more neurofibromas of any type or one plexiform neurofibroma; axillary or inguinal freckling; optic glioma; two or more Lisch nodules of the iris; a distinctive osseous lesion, such as sphenoid wing dysplasia or pseudarthrosis; or a first-degree relative diagnosed as having NF1 according to the preceding criteria. 3 It has been suggested that a pathogenic mutation in the NF1 gene be added to the list of diagnostic criteria. 4 The most common complications of NF1 are included in the previously listed diagnostic criteria. Additional features include short stature, scoliosis, headache, speech disorders, attention deficit disorder and attention-deficit/ hyperactivity disorder, and learning disabilities. Rare complications, affecting Ͻ5% of patients, include epilepsy, hydrocephalus, cardiovascular problems, and dystrophic scoliosis. 5 The lifetime risk of malignant tumors arising from peripheral nerves is estimated to be 10% to 13%. 6 The pathoetiology of the complications in NF1 is, however, largely unknown. Genetic BackgroundNF1 is caused by mutations in the NF1 gene that encodes the tumor suppressor protein neurofibromin. 7,8 The NF1 gene is located on chromosome band 17q11.2, spanning approximately 280 kb of genomic DNA, and is composed of 57 constitutive exons and 4 alternatively spliced exons (9a, 10a2, 23a, and 48a). 9 Howeve...

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“…Mast cells haploinsufficient for the NF1 gene infiltrated into NFs in response to KIT ligand and exhibited potency to proliferate. Precise etiopathogenesis of CALMs remains obscure, but it has been suggested that melanocyte density is increased within CALMs [20]. Also, somatic mutation analysis yielded two NF1 hits in melanocytes isolated from CALMs [21].…”

Section: Resultsmentioning

confidence: 99%

Vitamin D3 and Neurofibromatosis Type 1

Nakayama¹

2017

A Critical Evaluation of Vitamin D - Clinical Overview

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Vitamin D3 (VD3) and its analogs have been shown to inhibit growth of various cell types found in neurofibromas and pigmented lesions of patients with neurofibromatosis type 1 (NF1). Excimer light irradiation at 150-300 mJ/cm 2 in combination with VD3 efficiently inhibited growth of cultured fibroblasts, mast cells, Schwann cells, and melanocytes. Long-term whole body irradiation with narrowband ultraviolet B (UVB) in patients with NF1 significantly increased serum levels of VD3, which was accompanied by a brightening of generalized skin hyperpigmentation. Irradiation with either laser or intense pulsed-radio frequency in combination with topical application of VD3 analogs yielded moderate to fair improvement of café-au-lait macules, small pigmented spots, and skin-fold freckling in NF1 patients. Thus, topical or systemic application of VD3 or one of its analogs may provide beneficial effects to treat skin lesions for patients with NF1.

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Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?

Cited by 55 publications

References 53 publications

Evolving Pattern with Age of Cutaneous Signs in Neurofibromatosis Type 1: A Cross-Sectional Study of 728 Patients

Evolving Pattern with Age of Cutaneous Signs in Neurofibromatosis Type 1: A Cross-Sectional Study of 728 Patients

The Pathoetiology of Neurofibromatosis 1

Vitamin D3 and Neurofibromatosis Type 1

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