Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. We report the clinical manifestations of two patients from a Japanese family with SEI caused by a hotspot mutation, p.Glu487Lys, in KRT2. In addition, we summarize previous reports on SEI patients with the identical mutation. One of the two patients had disease onset at the age of 7 months. The other patient\'s age of onset is unknown, but it was in childhood. Neither of the two patients showed erythroderma. To perform deep phenotyping, we studied the age of onset and the frequency of erythroderma in 34 reported SEI cases with the p.Glu487Lys mutation, including the present cases. Among the cases with sufficient clinical information, 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.

A 14-year-old girl who reported generalized scaling and hyperkeratosis since age 1 year presented with severe pruritus of several months\' duration. Scabies mites were detected, and molecular genetic analysis subsequently revealed a rare pathogenic variant in the keratin 2 (KRT2) gene, confirming a diagnosis of superficial epidermolytic ichthyosis. Treatment with oral ivermectin led to complete remission of symptoms. Disorders of keratinization can mimic clinical signs of scabies, leading to a delay in diagnosis.

Superficial epidermolytic ichthyosis (formerly Ichthyosis bullosa of Siemens) is an uncommon condition caused by dominant mutations in KRT2 encoding keratin 2. Epidermolytic epidermal nevus due to somatic mutations in KRT2 is even rarer. Here, we report the third case of KRT2-associated epidermal nevus and review the literature.

Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation.

Superficial epidermolytic ichthyosis (SEI), known as ichthyosis bullosa of Siemens (IBS; OMIM No. 146800) before, is a type of keratinopathic ichthyosis due to the KRT2 mutations (NM_000423.3; OMIM No. 600194). Here, we report the first case of SEI caused by a KRT2 mosaic mutation.
We presented the clinical data of a 5-year-old Chinese boy who suffered from SEI. The histopathological examination and immunofluorescence were performed to rule out immunobullous skin diseases and diseases with subepidermal blisters. Genomic DNA samples were extracted from the lesion tissue and next-generation sequencing was performed. We also confirmed the variant allele frequency (VAF) in different tissues by an Ultra-Deep Sequencing technology.
The patient presented with blisters on the lower extremities and linear, superficially hyperkeratotic lesions. Immunofluorescence of IgG, IgA, IgM, C3, C4, and C1q were negative, and the histopathological results showed intraepidermal blisters containing lymphocytes and eosinophils. A heterozygous missense mutation, c.G1459A (p. Glu487Lys), in exon 7 of the KRT2 gene was detected at a 31.17% allele frequency. The same mutation p. Glu487Lys has been described several times in the literature.
Thus, in our patient, the mosaic mutation explains the blaschkoid ichthyosiform phenotype. To our knowledge, this is the first case of SEI with a KRT2 mosaic mutation.

In this paper, the authors report a case of an 11-year-old boy with epidermolytic ichthyosis who presented with multiple scattered erosions and typical hyperkeratotic plaques over the face, upper and lower extremities, the trunk, palms and soles. Family history revealed an affected older male sibling and an affected first-degree female relative. In addition, there was a positive history of generations of consanguinity in the patient\'s family pedigree, increasing the probability of an autosomal recessive inheritance. The clinical diagnosis was confirmed by histopathology; however, mutations in the keratin 1 and 10 genes were absent. This case report addresses the importance of establishing correct diagnosis and mode of inheritance, with literature review of genetic mutations, possible differential diagnosis and the most common and successful treatment modalities for epidermolytic ichthyosis.