Withdrawn:
            Skin fragility caused by biallelic
            KRT10
            mutations: an intriguing form of self‐improving epidermolytic ichthyosis

Epidermolytic Ichthyosis (EI) is a rare non-syndromic keratinopathic ichthyosis without definitive treatment. This is a case of EI in a 5-year-old Filipino female who presented with hyperkeratotic scales sparing the palms and soles. Histopathology revealed epidermolytic hyperkeratosis. A trial of treatment with isotretinoin 0.3 mg/kg/day, together with keratolytic agents, urea lotion and lactic acid lotion, resulted in a marked decrease in the thickness of the scales and odor. Interestingly, rebound effects were noted at 0.6 mg/kg/day. Taking into account that EI presents with more skin fragility compared to non-EHK ichthyosis, the authors surmise that there may be a smaller treatment window for patients with EI, which is notably lower than recommended for ichthyosis in general.

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Management of Epidermolytic Ichthyosis in the Newborn

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.35.1.19 ◽

2016 ◽

Vol 35 (1) ◽

pp. 19-30 ◽

Cited By ~ 6

Author(s):

Mondell Avril ◽

Cheryl Riley

Keyword(s):

Multidisciplinary Approach ◽

Autosomal Dominant ◽

Ethical Issues ◽

Successful Management ◽

Newborn Period ◽

Case Presentation ◽

Bullous Disease ◽

Epidermolytic Ichthyosis ◽

Skin Fragility ◽

Keratin 1

AbstractEpidermolytic ichthyosis (EI) is a rare autosomal dominant genodermatosis that presents at birth as a bullous disease, followed by a lifelong ichthyotic skin disorder.1 Essentially, it is a defective keratinization caused by mutations of keratin 1 (KRT1) or keratin 10 (KRT10) genes, which lead to skin fragility, blistering, and eventually hyperkeratosis. Successful management of EI in the newborn period can be achieved through a thoughtful, directed, and interdisciplinary or multidisciplinary approach that encompasses family support. This condition requires meticulous care to avoid associated morbidities such as infection and dehydration. A better understanding of the disrupted barrier protection of the skin in these patients provides a basis for management with daily bathing, liberal emollients, pain control, and proper nutrition as the mainstays of treatment. In addition, this case presentation will include discussions on the pathophysiology, complications, differential diagnosis, and psychosocial and ethical issues.

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Faculty Opinions recommendation of Homozygous nonsense mutation in DSC3 resulting in skin fragility and hypotrichosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738390011.793578032 ◽

2020 ◽

Author(s):

Takashi Hashimoto

Keyword(s):

Nonsense Mutation ◽

Skin Fragility ◽

Homozygous Nonsense Mutation

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Ichthyoses—A Clinical and Pathological Spectrum from Heterogeneous Cornification Disorders to Inflammation

Dermatopathology ◽

10.3390/dermatopathology8020017 ◽

2021 ◽

Vol 8 (2) ◽

pp. 107-123

Author(s):

Dieter Metze ◽

Heiko Traupe ◽

Kira Süßmuth

Keyword(s):

Stratum Granulosum ◽

Internal Organs ◽

Histopathologic Diagnosis ◽

Epidermolytic Ichthyosis ◽

Life Threatening ◽

Keratinization Disorders ◽

Gene Defects ◽

Immunohistochemical Methods

Ichthyoses are inborn keratinization disorders affecting the skin only (non-syndromic) or are associated with diseases of internal organs (syndromic). In newborns, they can be life-threatening. The identification of the gene defects resulted in reclassification and a better understanding of the pathophysiology. Histopathologic patterns include orthohyperkeratosis with a reduced or well-developed stratum granulosum, hyperkeratosis with ortho- and parakeratosis with preserved or prominent stratum granulosum, and epidermolytic ichthyosis. Another pattern features “perinuclear vacuoles and binucleated keratinocytes”, which is associated with keratin mutations. Some ichthyoses are histologically defined by psoriasis-like features, and distinct subtypes show follicular hyperkeratosis. In addition to histological and immunohistochemical methods, these patterns allow a better histopathologic diagnosis.

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Isoform-Specific Roles of Mutant p63 in Human Diseases

Cancers ◽

10.3390/cancers13030536 ◽

2021 ◽

Vol 13 (3) ◽

pp. 536

Author(s):

Christian Osterburg ◽

Susanne Osterburg ◽

Huiqing Zhou ◽

Caterina Missero ◽

Volker Dötsch

Keyword(s):

Cleft Lip ◽

Ectodermal Dysplasia ◽

Skin Development ◽

Disease Mechanisms ◽

Skin Fragility ◽

Cleft Lip Palate ◽

Life Threatening ◽

Functional Consequences ◽

Development And Differentiation

The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the DNA binding domain cause Ectrodactyly, Ectodermal Dysplasia, characterized by limb deformation, cleft lip/palate, and ectodermal dysplasia while mutations in in the C-terminal domain of the α-isoform cause Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility, severe, long-lasting skin erosions, and cleft lip/palate. The molecular disease mechanisms of these syndromes have recently become elucidated and have enhanced our understanding of the role of p63 in epidermal development. Here we review the molecular cause and functional consequences of these p63-mutations for skin development and discuss the consequences of p63 mutations for female fertility.

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A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops

Genes ◽

10.3390/genes12050716 ◽

2021 ◽

Vol 12 (5) ◽

pp. 716

Author(s):

Daniele Castiglia ◽

Paola Fortugno ◽

Angelo Giuseppe Condorelli ◽

Sabina Barresi ◽

Naomi De Luca ◽

...

Keyword(s):

Amniotic Membrane ◽

Epidermolysis Bullosa ◽

Ocular Involvement ◽

Human Amniotic Membrane ◽

Vitro Assay ◽

Junctional Epidermolysis Bullosa ◽

Mucosal Involvement ◽

Skin Fragility ◽

Laminin 332

Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C>G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.

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