Epidermolysis bullosa simplex (EBS) is a clinically and genetically heterogeneous skin disorder characterized by recurrent blistering of the skin following minor physical trauma as a result of cytolysis within basal epidermal cells. Most forms show autosomal dominant inheritance. ... Epidermolysis bullosa simplex (EBS) is a clinically and genetically heterogeneous skin disorder characterized by recurrent blistering of the skin following minor physical trauma as a result of cytolysis within basal epidermal cells. Most forms show autosomal dominant inheritance. The 3 main types include the generalized Koebner form, the more severe generalized Dowling-Meara form (131760), and the localized, mild Weber-Cockayne form (131800) (Fine et al., 2008). All 3 forms can be caused by mutation in the KRT5 or the KRT14 gene. See 601001 for a rare autosomal recessive form caused by mutation in the KRT14 gene. Davison (1965) referred to generalized distribution of bullous vesicles as epidermolysis simplex bullosa. The condition in which bullae were limited to the hands and feet was referred to as the Cockayne type of epidermolysis bullosa (131800). On the basis of an extensive study in Norway and review of the literature, Gedde-Dahl (1971) arrived at a classification of epidermolysis bullosa. EB simplex in this classification encompassed disorders characterized by bulla formation within the epidermis, basal cell vacuolization, and dissolution of tonofibrils on electron microscopy. The generalized Koebner form and the localized Weber-Cockayne type were believed to be allelic. Gedde-Dahl (1981) recognized at least 16 varieties of epidermolysis bullosa and suggested that dominant EB simplex can be clinically and genetically divided into at least 4 types: the generalized Koebner type, the localized Weber-Cockayne type, the mild Ogna type with fragile skin (131950), and a form with mottled pigmentation (131960). Fine et al. (1991) provided a revised classification of the subtypes of inherited epidermolysis bullosa based on clinical and laboratory criteria.
Passarge (1965) observed 21 affected persons in 4 generations of a family with generalized epidermolysis bullosa simplex. The inheritance pattern was autosomal dominant.
Hacham-Zadeh et al. (1988) described a large Arab family originating from Jerusalem in ... Passarge (1965) observed 21 affected persons in 4 generations of a family with generalized epidermolysis bullosa simplex. The inheritance pattern was autosomal dominant. Hacham-Zadeh et al. (1988) described a large Arab family originating from Jerusalem in which 38 affected individuals spanning 4 generations had EBS. Onset occurred between birth and 2 weeks of age. The main clinical features were bullae, generalized, solitary, and in groups, with predilection to the skin of the palms and soles. Mild to moderate patchy hyperkeratosis of the palms and soles was found in 5 affected members of the family. Blisters in oral mucous membranes were noted and found in summer and in periods of fever. Hair, teeth, and nails were normal. Improvement was noted by progression of age from 5 to 23 years, and by some in summer and by others in winter. Ultrastructural studies from a fresh blister disclosed intraepidermal blister via cytolysis of basal cell cytoplasm. The pedigree indicated transmission of an autosomal dominant gene. However, in 1 instance, affected first cousins were married and all 6 of their offspring were affected. There was marked intrafamilial variability. Although the family was originally thought to have the Dowling-Meara form of EBS, Stephens et al. (1995) reclassified the phenotype as the Koebner type based on the lack of keratin filament clumping on electron microscopy.
Livingston et al. (2001) reported a patient who presented at 3 to 4 days of age with widespread generalized blistering. Painful hyperkeratosis of the palms and soles developed in his teen years, whereas blistering improved somewhat with age. ... Livingston et al. (2001) reported a patient who presented at 3 to 4 days of age with widespread generalized blistering. Painful hyperkeratosis of the palms and soles developed in his teen years, whereas blistering improved somewhat with age. As an adult, he continued to get occasional blisters in the mouth and cutaneous blisters with increased heat and/or activity. His skin examination was striking for severe palmoplantar keratosis, underlying erythema in a 'glove and moccasin' distribution, and limited range of motion in the fingers. There was no scarring and no significant nail changes. Clinical, histologic, and ultrastructural features were consistent with a diagnosis of generalized EBS (Koebner subtype). Genetic analysis identified a heterozygous nonsense mutation in the KRT5 gene (K472X; 148040.0016), predicting the synthesis of a truncated keratin-5, missing the entire tail domain and a highly conserved motif in the central rod. Ultrastructural analysis of the patient's nonhyperkeratotic skin was remarkable for basal keratinocytes with dense and irregular keratin filaments proximal to the basement membrane. The occurrence of severe palmoplantar hyperkeratosis suggested that the keratin-5 tail domain may have important functions in palmoplantar tissues.
In a family with the generalized form of epidermolysis bullosa simplex, Bonifas et al. (1991) found linkage to markers on chromosome 17 and identified a point mutation in the KRT14 gene (L384P; 148066.0001).
In affected members ... In a family with the generalized form of epidermolysis bullosa simplex, Bonifas et al. (1991) found linkage to markers on chromosome 17 and identified a point mutation in the KRT14 gene (L384P; 148066.0001). In affected members of a large Irish family with generalized EBS, Humphries et al. (1993) identified a heterozygous mutation in the KRT14 gene (M272R; 148066.0007). In affected members of a large Finnish family with the generalized Koebner type of EBS in which Ryynanen et al. (1991) found linkage to 12q, Dong et al. (1993) identified a heterozygous mutation in the KRT5 gene (L463P; 148040.0002). In affected members of a family with autosomal dominant epidermolysis bullosa simplex, Stephens et al. (1995) identified a heterozygous mutation in the KRT5 gene (K173N; 148040.0006). One family member was homozygous for the K173N allele, having inherited it from each of her affected first-cousin parents. However, this patient showed no significant differences in either the clinical severity or the ultrastructural organization of the homozygous keratin intermediate filament cytoskeleton. These data demonstrated that the K173N mutation behaves as a fully dominant allele. Among 18 families with various forms of EBS, Pfendner et al. (2005) identified KRT5 mutations in 7 probands and KRT14 mutations in 11 probands, indicating that mutations in either gene can result in EBS at approximately equal frequencies. A large number (15 of 18) were de novo mutations. The clinical spectrum was highly variable.