RESUMO
BACKGROUND: Spontaneous lightening of congenital melanocytic naevi (CMN) has not been studied systematically. Final colour is considered an important outcome after superficial removal techniques such as curettage, dermabrasion or laser ablation, and is often compared with colour at birth. OBJECTIVES: To quantify the natural history of CMN lightening over time, and explore phenotypic and genotypic predictors of colour change. METHODS: A longitudinal cohort study was undertaken of 110 patients with CMN (mean follow-up 5·3 years). Accurate colour-space measurements were taken from professional serial photographs of CMN and normal skin. Changes in colour over time were modelled using multiple logistic regression, against phenotypic and genotypic variables. RESULTS: Lightening of CMN was significantly associated with lighter normal skin colour (P < 0·001) and with MC1R variant alleles (red/blonde hair gene) (P < 0·001), but not with CMN colour in the first 3 months of life, NRAS genotype or projected adult size of CMN. Importantly, the final colours of adjacent treated and untreated areas of CMN were indistinguishable. CONCLUSIONS: Final CMN colour in childhood is related to the genetically determined skin colour of the individual, is unrelated to the colour of CMN at birth, and is unaffected by superficial removal. What's already known about this topic? Final colour of congenital melanocytic naevi (CMN) is considered an important outcome after superficial removal techniques such as curettage, dermabrasion or laser ablation, and is often compared with colour at birth. The phenomenon of spontaneous lightening in CMN, in which naevi lighten gradually and sometimes dramatically during childhood, has been described but not systematically studied. What does this study add? Final CMN colour in childhood is significantly associated with the individual's normal skin colour, and with MC1R genotype, and is therefore genetically determined. Final CMN colour is not predictable from CMN colour in the first 3 months of life. Superficial removal techniques do not alter the final colour of CMN.
Assuntos
Nevo Pigmentado , Neoplasias Cutâneas , Adulto , Cor , Humanos , Recém-Nascido , Estudos Longitudinais , Nevo Pigmentado/genética , Nevo Pigmentado/cirurgia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/cirurgia , Pigmentação da PeleRESUMO
BACKGROUND: Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which can help shape management. OBJECTIVES: To characterize the frequency of different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype and genotype-outcome associations. METHODS: We conducted a large cohort study in which we undertook MC1R genotyping from blood, and high-sensitivity genotyping of NRAS and BRAF hotspots in 156 naevus biopsies from 134 patients with CMN [male 40%; multiple CMN 76%; projected adult size (PAS) > 20 cm, 59%]. RESULTS: Mosaic NRAS mutations were detected in 68%, mutually exclusive with BRAF mutations in 7%, with double wild-type in 25%. Two separate naevi were sequenced in five of seven patients with BRAF mutations, confirming clonality. Five of seven patients with BRAF mutations had a dramatic multinodular phenotype, with characteristic histology distinct from classical proliferative nodules. NRAS mutation was the commonest in all sizes of CMN, but was particularly common in naevi with PAS > 60 cm, implying more tolerance to that mutation early in embryogenesis. Facial features were less common in double wild-type patients. Importantly, the incidence of congenital neurological disease, and apparently of melanoma, was not altered by genotype; no cases of melanoma were seen in BRAF-mutant multiple CMN, however, this genotype is rare. CONCLUSIONS: CMN of all sizes are most commonly caused by mutations in NRAS. BRAF is confirmed as a much rarer cause of multiple CMN, and appears to be commonly associated with a multinodular phenotype. Genotype in this cohort was not associated with differences in incidence of neurological disease in childhood. However, genotyping should be undertaken in suspected melanoma, for guidance of treatment. What's already known about this topic? Multiple congenital melanocytic naevi (CMN) have been shown to be caused by NRAS mosaic mutations in 70-80% of cases, by BRAF mosaicism in one case report and by inference in some previous cases. There has been debate about genotypic association with different sizes of CMN, and no data on genotype-outcome. What does this study add? NRAS mosaicism was found in 68%, BRAF in 7% and double wild-type in 25% of cases of CMN. NRAS was the commonest mutation in all sizes of CMN, but was nearly universal in projected adult size > 60 cm. BRAF is often associated with a distinct multinodular clinical/histological phenotype. Adverse outcomes did not differ between genotypes on current numbers.
Assuntos
Nevo Pigmentado , Neoplasias Cutâneas , Adulto , Estudos de Coortes , Genótipo , Humanos , Masculino , Mutação/genética , Nevo Pigmentado/genética , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genéticaAssuntos
Genes Recessivos/genética , Ictiose Lamelar/genética , Síndrome de Prader-Willi/genética , Esfingosina N-Aciltransferase/genética , Dissomia Uniparental , Criança , Cromossomos Humanos Par 15/genética , Análise Mutacional de DNA , Feminino , Homozigoto , Humanos , Ictiose Lamelar/diagnóstico , Síndrome de Prader-Willi/diagnósticoAssuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Colorretais/diagnóstico , Proteínas de Ligação a DNA/genética , Melanose/etiologia , Síndromes Neoplásicas Hereditárias/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Colorretais/genética , Consanguinidade , Feminino , Humanos , Lactente , Melanose/genética , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neurocutâneas/diagnóstico , Síndromes Neurocutâneas/genéticaAssuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Mutação em Linhagem Germinativa/genética , Anormalidades da Pele/genética , Feminino , Humanos , Masculino , Mosaicismo , Fenótipo , Anormalidades da Pele/etnologia , Zigoto/fisiologiaAssuntos
Neoplasias Faciais/genética , Mosaicismo , Mutação de Sentido Incorreto/genética , Síndrome de Proteu/genética , Proteínas Proto-Oncogênicas c-akt/genética , Bochecha , Pré-Escolar , Feminino , Heterozigoto , Humanos , Perna (Membro) , Imageamento por Ressonância Magnética , Pescoço , Nevo Pigmentado/genética , FenótipoRESUMO
UNLABELLED: Reconstructive laryngeal surgery has been very successful in the treatment of laryngotracheal stenosis. Traditionally authors have used survival and decannulation rates as markers of success. OBJECTIVE: To evaluate the outcome of paediatric laryngotracheal surgery from the parents perspective. METHOD: Retrospective audit of all children undergoing laryngotracheal reconstruction or cricotracheal resection for laryngotracheal stenosis in a three year period at the Royal Hospital for Sick Children, Glasgow. An open-ended questionnaire was used to assess parental concerns regarding their child's airway, post-operative results and the current status of their voice, breathing and swallowing. RESULTS: 30 patients were eligible for the inclusion of which there were 17 responses (56%). The most common concerns pre-operatively were difficulty breathing, tracheostomy and survival. Post-operatively parents felt that breathing, voice and a reduction in the number of lower respiratory tract infections were the main improvements. We also identified the high level of importance that the parents assigned to their child's independence and ability to lead a normal life. CONCLUSION: This study has given us a unique insight into the concerns of parents who have children with laryngotracheal stenosis. It has also allowed us to evaluate our post-operative results from a qualitative perspective through the eyes of the parents.