Gene detection in a family with monilethrix and treatment with 5% topical minoxidil.

OBJECTIVE: To determine the causative gene mutation in a family with monilethrix and observe the therapeutic effect of 5% topical minoxidil. METHOD: Clinical data from a family with monilethrix were collected. Peripheral blood samples were taken from the proband, the parents, and 100 unrelated healthy controls. Genomic DNA was extracted. The genetic variation sites were screened with exome sequencing and verified by Sanger sequencing. The proband was treated with 5% topical minoxidil (1 mL twice daily). Hair quality was examined by dermoscopy before and after treatment. RESULTS: The proband and her father have the heterozygous missense variant c.1204G > A (p.E402K) in exon 7 of the KRT86 gene. However, the mutation was not found in the mother and healthy controls. The proband was treated with 5% topical minoxidil. Hair density and hair shaft quality improved significantly after 6 months of treatment. No adverse events occurred during treatment. CONCLUSION: This study shows that p.E402K is a mutation "hot spot" in patients with autosomal dominant monilethrix in China. Treatment with 5% topical minoxidil, is safe and effective.

Autosomal recessive monilethrix: Novel variants of the DSG4 gene in three Chinese families.

BACKGROUND: Monilethrix is a rare hereditary hair loss disorder characterized by hair fragility and beaded hair shaft alterations. Monilethrix is classically inherited in an autosomal dominant (AD) fashion caused by variants in the hair keratin genes KRT81, KRT83, or KRT86. Interestingly, an autosomal recessive (AR) form of monilethrix with variants in DSG4 gene has also been reported in recent years. OBJECTIVE: To identify causative variants in Chinese patients with autosomal recessive (AR) form of monilethrix. METHODS: Three families with AR form of monilethrix were observed and sequence variant analysis of DSG4 was performed by polymerase chain reaction (PCR), quantitative real-time PCR, and DNA sequencing. RESULTS: All the patients had sparse, fragile hair involving the scalp, eyebrows, and eyelashes with keratotic follicular papules and pruritus since birth. Atypical-beaded hairs and broken hair shaft fragments were identified in all the patients under dermoscopy. Heterozygous variants c.837del and c. 2389C > T, a homozygous splice site variant c.2355 + 1G > A, and a homozygous 48,644 bp large deletion variant g.31381440_31430084del in the DSG4 gene were identified and verified in the families. CONCLUSION: This report provided further evidence for the phenotypic spectrum and clinical features of, and the expanded variant database of AR form of monilethrix.

Review of oral minoxidil as treatment of hair disorders: in search of the perfect dose.

Topical minoxidil has been used for many years as treatment for different hair disorders. Even though it is an effective therapy, many patients show poor compliance due to the cosmesis, cost and side-effects. During the last few years, low-dose oral minoxidil has proven to be an alternative for patients with alopecia. We performed a literature search including all the articles that used oral minoxidil as a primary treatment in various hair diseases in order to evaluate the efficacy and safety of low-dose oral minoxidil as an alternative to topical minoxidil. Androgenetic alopecia was the most common studied condition, but others included telogen effluvium, tractional alopecia, postchemotherapy-induced alopecia, monilethrix, loose anagen hair syndrome, alopecia areata and scarring alopecias (frontal fibrosing alopecia and lichen planopilaris). Larger randomized comparative studies including standardized objective measurements should be done in order to clarify the best treatment protocol, including dosage and treatment duration. Oral minoxidil has proven to be a successful and well-tolerated alternative for patients with hair loss, including those with poor adherence to other therapies. Different dosing regimens have been utilized in scarring and non-scarring alopecia, varying from 0.25 to 5 mg daily. Higher doses have not been studied in men or women. Available literature suggests women require lower doses, from 0.25 to 2.5 mg daily, while men require higher doses for maximal efficacy, from 1.25 to 5 mg a day.

Nanomechanical properties of Monilethrix affected hair are independent of phenotype.

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.

Trichoscopy in Hair Shaft Disorders.

Trichoscopy allows analyzing the structure and size of growing hair shafts in their natural environment in children and adults. The method replaces light microscopy, which requires pulling of multiple hairs for investigation. In monilethrix, trichoscopy shows uniform elliptical nodosities with intermittent constrictions. In trichorrhexis nodosa nodular thickenings along hairs shafts are visible (low magnification) or splitting into numerous small fibers along the hair shaft may be observed (high magnification). In trichorrhexis invaginata (bamboo hair) the hair shaft telescopes into itself at several points along the shaft. Trichoscopy shows small nodules along the shaft. Hairs bend and break in these diseases. Trichoscopy of pili torti shows twists of hair shafts along their long axis. In pili annulati hair shafts with alternating white and dark bands are visible. In woolly hair the examination demonstrates hair shafts with waves at very short intervals. For trichothiodystrophy polarized trichoscopy should be used. In ectodermal dysplasias, trichoscopy shows a variety of hair abnormalities, but the most characteristic finding is hair shaft pigmentation heterogeneity.

[Monilethrix is a hereditary hair shaft disorder].

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.

Value of dermoscopy for the diagnosis of monilethrix.

Monilethrix is a rare genodermatosis characterized by a hair shaft dysplasia responsible for hypotrichosis. We report the case of a child with monilethrix with no associated cases in the family. Trichoscopy facilitated the diagnosis. A 2-year-old boy presented with diffuse alopecia and persistent fragile hair for several months. Clinical examination revealed alopecia with hairs broken several millimeters from the scalp. Trichoscopy revealed zones of dystrophic constriction of the hair shaft, separated at regular intervals by elliptical nodes of normal thickness, giving a "necklace" appearance. The diagnosis of monilethrix was made on the basis of these specific features. The diagnosis of monilethrix was more difficult to establish in our patient owing to the absence of any familial cases.

Recessive progressive symmetric erythrokeratoderma results from a homozygous loss-of-function mutation of KRT83 and is allelic with dominant monilethrix.

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.

Journey toward unraveling the molecular basis of hereditary hair disorders.

Recent advances in molecular genetics have led to the identification of many genes expressed in hair follicle (HF), while the precise roles of these genes in the HF have not completely been disclosed. Using the methods of forward genetics, we and others have recently identified a series of genes responsible for hereditary hair disorders in humans, including monilethrix, woolly hair, and various ectodermal dysplasia syndromes. Furthermore, expression and functional analyzes have gradually revealed that these genes are directly or indirectly related with each other. As such, the journey toward unraveling the molecular basis of hereditary hair disorders will contribute to better understanding of the complex mechanisms for HF morphogenesis and development in humans.