Epidermolytic hyperkeratosis: generalized form in children from parents with systematized linear form

Abstract

Two unrelated families are presented in both of which a child with generalized epidermolytic hyperkeratosis (congenital bullous ichthyosiform erythroderma) had a parent with linear epidermolytic hyperkeratosis (epidermolytic epidermal naevus). Light and electron microscopy of skin biopsies of lesions from the children and parents showed typical epidermolytic hyperkeratosis. Gonadal mosaicism in patients with linear epidermolytic hyperkeratosis may be responsible for transmission of the abnormality to the offspring.

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept

“…Later it was reported that patients with a segmental manifestation of an autosomal dominant skin disease had an increased risk of transmitting the trait in the ordinary, nonsegmental form to their children (16,17). Such observations implied that the underlying mutation could also affect the germline in the form of gonadal mosaicism.…”

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…[72][73][74] Because recognition of this risk is important for genetic counseling, epidermolytic nevi have been included (in brackets) in the classification of KPI (Table II).…”

Phenotypic Heterogeneity in Bullous Congenital Ichthyosiform Erythroderma

“…2,3 It is known that the offspring of patients with an epidermolytic-type of epidermal nevi may have generalized BCIE. 4,5 Paller et al 6 and Moss et al 7 showed that epidermal nevus represents somatic mosaicism for a keratin 10 gene mutation, which may produce generalized BCIE in the next generation if germline cells carry the mutation. Although theoretically a possibility, keratin 1 gene mosaicism has not yet been described as a cause of epidermal nevi.…”

“…4,5 Recently, Paller et al 6 demonstrated the same keratin gene mutations in the lesional keratinocytes of the epidermal nevi of parents and in the DNA of their offspring with BCIE. These results provide evidence that a postzygotic mutation can be passed on to the next generation in BCIE.…”

“…In fact, review of previously described cases showed that distribution along Blaschko lines is not characteristic of patients with mosaic BCIE and extensive phenotypic involvement. 4 Clearly, the mosaicism affected germline cells in that the mother was able to transmit the gene mutation to the proband as a generalized mutation. Many families with BCIE show phenotypic variability.…”