Bullous diseases caused by gene mutations: from epidermolytic hyperkeratosis to a novel variant of epidermolysis bullosa simplex.

Introduction: Mutations in the gene encoding keratin 1 cause epidermolytic hyperkeratosis characterized by blistering in the neonatal period followed by ichthyotic hyperkeratosis in childhood and adolescent life. We observed a spectrum of clinical manifestations of blistering disorders caused by different mutations in the same gene.

Aim: To analyse the phenotypic spectrum of blistering disorders caused by the mutations.

Material And Methods: Four patients with an epidermal barrier defect manifesting as blistering with the mutations were included to the study. The clinical course of the disease was analysed, histology, immunofluorescence and electron microscopic examinations were performed.

Results: An adult patient with severe ichthyosis with p.Asn188Lys mutation in exon 1 of who occasionally develops blisters in adolescence represents epidermolytic hyperkeratosis, a newborn child who died 4 days after birth due to disruption of the epidermal barrier (extensive blister and erosions) with mutation p.Ser193Pro in the gene and two adult sisters harbouring heterozygous mutation c.591+1A>G in the gene who present superficial blisters induced by mild trauma from the birth up to adolescent life without ichthyosis suggesting the diagnosis of epidermolysis bullosa simplex. Histopathology in all adult patients showed cytoplasm disruption in keratinocytes of the stratum spinosum with keratohyalin granule-like structures and, on the ultrastructural level, the presence of keratin clumping confirming the pathology of keratin intermediate filaments.

Conclusions: This study extends the knowledge of the clinical spectrum for the gene mutations. This is the first description of familial dominant epidermolysis bullosa simplex linked to the mutation.