RESUMO
Utilising the AFM nanoindentation technique for the study of hair cross- and longitudinal sections, the mechanical anisotropy of human hair fibres affected by a rare congenital condition, Monilethrix, has been investigated for the first time. Supported by X-ray microdiffraction data, and applying a model based on an ideal composite material consisting of rods (KIFs) and matrix (KAPs) to Monilethrix affected fibres, it has been shown that the results could be grouped into clearly different classes, namely: almost isotropic behaviour for Monilethrix affected hairs and anisotropic behaviour for Control hair. Moreover, AFM nanoindentation of hair cross sections has demonstrated, also for the first time that hairs affected by Monilethrix have a continuous, and not periodic, weakness within the cortex. This has been attributed to disruptions in the KIF-KIF, KIF-intermacrofibrillar matrix or KIF-desmosome complexes within the hair shaft, as suggested by X-ray microdiffraction examination. Hairs from a patient exhibiting no obvious phenotype exhibited similar mechanical weakness despite the otherwise normal visual appearance of the fibre. This further supports a hypothesis that the beaded appearance of Monilethrix hair is a secondary factor, unrelated to the inherent structural weakness.
Assuntos
Cabelo/patologia , Monilétrix/patologia , Humanos , Fenótipo , Raios XRESUMO
Monilethrix is a rare genodermatosis with high penetrance and variable expressivity. This is a case report of a Danish family with varying phenotypical presentations. The family members were diagnosed using dermatoscopy and microscopy, which were subsequently supported by gene sequence analysis. No cure of monilethrix exists, but a single case report shows promising results using low dosage of oral minoxidil. Reducing hair dressing trauma to diminish weathering remains the best prophylaxis.
Assuntos
Monilétrix/diagnóstico , Adulto , Criança , Pré-Escolar , Família , Feminino , Testes Genéticos , Humanos , Masculino , Monilétrix/genética , Monilétrix/patologiaRESUMO
BACKGROUND: Progressive symmetric erythrokeratoderma (PSEK) is a rare skin disorder characterised by symmetrically distributed demarcated hyperkeratotic plaques, often with associated palmoplantar hyperkeratosis, with new plaques appearing over time. Most cases are inherited in an autosomal dominant manner, although a few cases exhibit apparent autosomal recessive inheritance. OBJECTIVE: To identify the gene underlying autosomal recessive PSEK in a large Pakistani kindred. METHODS: We first carried out autozygosity mapping using microsatellite markers in candidate regions of the genome. We then carried out exome sequencing of five family members, autozygosity mapping and mutation analysis using the exome data and verification by Sanger sequencing. RESULTS: Autozygosity mapping and exome sequencing identified a homozygous frameshift deletion (c.811delA; p.Ser271fs) in KRT83, which co-segregated with the PSEK phenotype in the family and which is expected to abolish keratin 83, a type II keratin of hair and skin. CONCLUSIONS: At least some cases of PSEK result from loss-of-function mutations in KRT83. Heterozygous missense substitutions in KRT83 have been implicated in autosomal dominant monilethrix, a rare hair disorder. Our findings indicate that at least some cases of autosomal recessive PSEK and autosomal dominant monilethrix are allelic, respectively resulting from loss-of-function and missense mutations in the KRT83 gene. Together, these findings indicate that different types of mutations in KRT83 can result in quite different skin and hair phenotypes.
Assuntos
Eritroceratodermia Variável/genética , Queratinas Específicas do Cabelo/genética , Queratinas Tipo II/genética , Monilétrix/genética , Alelos , Eritroceratodermia Variável/patologia , Exoma/genética , Feminino , Cabelo/metabolismo , Cabelo/patologia , Heterozigoto , Homozigoto , Humanos , Masculino , Monilétrix/patologia , Mutação de Sentido Incorreto , Paquistão , Linhagem , Fenótipo , Deleção de Sequência , Pele/metabolismo , Pele/patologiaRESUMO
BACKGROUND: Localized autosomal recessive hypotrichosis (LAH) is an inherited rare disease caused by DSG4 mutations, characterized by short, sparse, brittle hair affecting restricted areas such as the scalp, trunk, and extremities. To date, DSG4 mutations have been reported in 14 pedigrees of LAH overlapping with monilethrix. METHODS: To clarify the etiology of hair defects for a 2-year-old Chinese girl, peripheral blood, skin, and hair samples were collected, and skin immunohistochemistry, electron microscopy (scanning and transmission types), Vivascope confocal microscopy, and DSG4 sequencing were investigated. RESULTS: The patient presented sparse hairs of various length and follicular hyperkeratotic papules. Eyebrows and lashes were also involved (broke or shed). The biopsy specimen revealed curled ingrown hair shafts within the hair follicle and keratin-filled hair follicles. Scanning electron microscopy revealed hair cuticle loosely and irregularly arranged, as well as a marked warping, curling, cracking, and detachment of hair cuticle. Transmission electron microscopy indicated notable dysadhesion between cells of the outer root sheath. A homozygous mutation A1103G in exon 8 of DSG4 was identified in the patient, resulting in the substitution of an aspartic acid by glycine (D323G) and reduced DSG4 expression in the affected scalp epidermis. CONCLUSIONS: The homozygous A1103G mutation in DSG4 was responsible for the disease development.
Assuntos
Desmogleínas/genética , Hipotricose/genética , Monilétrix/genética , Mutação de Sentido Incorreto , Pré-Escolar , Feminino , Cabelo/ultraestrutura , Humanos , Hipotricose/complicações , Hipotricose/patologia , Monilétrix/complicações , Monilétrix/patologiaRESUMO
Monilethrix is a rare hereditary condition generally considered to be an autosomal dominant disorder with variable penetrance. A case of a 6-year-old girl without a familial background for this disease is reported. The diagnosis was made by optic microscopy and dermoscopy. A therapeutic trial with topical minoxidil was conducted.
Assuntos
Dermoscopia/métodos , Monilétrix/patologia , Administração Cutânea , Criança , Feminino , Humanos , Hipotricose/tratamento farmacológico , Hipotricose/patologia , Minoxidil/uso terapêutico , Monilétrix/tratamento farmacológico , Resultado do TratamentoRESUMO
Monilethrix is a rare hereditary condition generally considered to be an autosomal dominant disorder with variable penetrance. A case of a 6-year-old girl without a familial background for this disease is reported. The diagnosis was made by optic microscopy and dermoscopy. A therapeutic trial with topical minoxidil was conducted.
Assuntos
Criança , Feminino , Humanos , Dermoscopia/métodos , Monilétrix/patologia , Administração Cutânea , Hipotricose/tratamento farmacológico , Hipotricose/patologia , Minoxidil/uso terapêutico , Monilétrix/tratamento farmacológico , Resultado do TratamentoAssuntos
Monilétrix/patologia , Alopecia/etiologia , Pré-Escolar , Consanguinidade , Diagnóstico Diferencial , Feminino , Humanos , IrmãosRESUMO
BACKGROUND: Monilethrix is an autosomal dominant hair disorder characterized clinically by alopecia and follicular papules. In this study, we collected a Han monilethrix family to detect the mutations in patients and investigated the correlation between the genotype and phenotype of monilethrix. METHODS: In this study, we identified a Chinese family with monilethrix through light microscopic and scanning electron microscopic (SEM) examination. Genomic DNA from peripheral blood samples was prepared. DNA samples from controls and monilethrix patients were subject to polymerase chain reaction (PCR) amplification. Two pairs of primers were used to amplify the seventh exon of KRT86. Mutation screening of the PCR products was detected using direct sequencing. RESULTS: Light microscopic examination showed a regular alternate enlargement and narrow area. SEM examination showed that part of the cuticle of the nodules shed and disappeared gradually in the narrow area with granular protrusions on the surface similar to the erosion-like structure. Parallel longitudinal ridge and groovepattern appeared, and the ridges varied in width, like dead wood. A heterozygous transversion mutation c.1204G > A (p.E402K) in the seventh exon of KRT86 was identified in both patients. CONCLUSIONS: The mutation of extron 7 of KRT86 identified plays a major role in the pathogenesis of this pedigree with monilethrix, and is a mutation hot spot of KRT86. Further research is needed to explore the relationship between the phenotype and the mutation of the type II hair keratin gene KRT86 of monilethrix.
Assuntos
Queratinas Específicas do Cabelo/genética , Queratinas Tipo II/genética , Monilétrix/genética , Mutação , Povo Asiático/genética , China/etnologia , Humanos , Microscopia Eletroquímica de Varredura , Monilétrix/etiologia , Monilétrix/patologiaRESUMO
A 4-year-old girl presented with sparse, brittle hair on her entire scalp and keratosis pilaris on the nape of her neck. Subtle microscopic and macroscopic diagnostic features presented a challenge for physicians. Only repeated, optimized light microscopy revealed the diagnosis of monilethrix, a rare genetic hair shaft disorder with a variable phenotypic expression and inheritance pattern. We provide a short overview of methods that maximize the diagnostic yield in a clinical setting and of light microscopy to reach a rapid and accurate diagnosis in difficult cases. We conclude with essential learning points, including a link to assistance with hair microscopy from a tertiary center.
Assuntos
Anormalidades Múltiplas/diagnóstico , Doença de Darier/diagnóstico , Dermoscopia/métodos , Sobrancelhas/anormalidades , Cabelo/patologia , Monilétrix/diagnóstico , Anormalidades Múltiplas/patologia , Pré-Escolar , Doença de Darier/patologia , Diagnóstico Diferencial , Sobrancelhas/patologia , Feminino , Humanos , Monilétrix/patologiaAssuntos
Anormalidades Congênitas/genética , Meato Acústico Externo/anormalidades , Queratinas Específicas do Cabelo/genética , Queratinas Tipo II/genética , Monilétrix/genética , Adulto , Povo Asiático/genética , China , Anormalidades Congênitas/patologia , Análise Mutacional de DNA , Orelha/anormalidades , Orelha/patologia , Feminino , Humanos , Masculino , Monilétrix/patologia , Mutação , LinhagemRESUMO
In literature many different therapies are proposed to treat Monilethrix, but a definitive therapy still doe not exist. We decided to treat four patients affected by Monilethrix, with topical minoxidil 2%, 1 ml night and day for 1 year. Minoxidil led to a an increase of normal hair shaft without any side effects in all the patients. Therefore topical minoxidil 2% could be considered a good therapy to treat Monilethrix.
Assuntos
Minoxidil/administração & dosagem , Monilétrix/tratamento farmacológico , Administração Tópica , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monilétrix/patologiaAssuntos
Monilétrix/patologia , Tricotilomania/diagnóstico , Criança , Saúde da Família , Feminino , Cabelo/patologia , HumanosRESUMO
A 3-year-old girl showed fine, sparse, and brittle scalp hair without signs of cicatricial cutaneous alterations. Dermoscopy as well as scanning electron microscopy revealed elliptical nodes as well as constricted regions along the hair shaft.