EPIDERMOLYSIS BULLOSA OF HANDS AND FEET
EBS, ACRAL FORM
Epidermolysis bullosa simplex of palms and soles
epidermolysis bullosa simplex, weber-cockayne type
EBS-loc
Epidermolysis bullosa simplex is a clinically and genetically heterogeneous skin disorder characterized by blistering of the skin following minor physical trauma as a result of cytolysis within the basal epidermal cells. Most forms show autosomal dominant inheritance. The ... Epidermolysis bullosa simplex is a clinically and genetically heterogeneous skin disorder characterized by blistering of the skin following minor physical trauma as a result of cytolysis within the basal epidermal cells. Most forms show autosomal dominant inheritance. The localized form is characterized by localized blistering primarily on the hands and feet (Pfendner et al., 2005). The other 2 main types of EBS include the milder generalized Koebner type (131900) and the more severe Dowling-Meara type (131760). All 3 forms can be caused by mutation in the KRT5 or KRT14 genes (summary by Fine et al., 2008).
Readett (1961) described a family in which 14 members in 5 generations had localized epidermolysis bullosa of the hands and feet inherited in an autosomal dominant pattern. Treatment with adrenosteroid depressed bulla formation, but recurrence occurred with the ... Readett (1961) described a family in which 14 members in 5 generations had localized epidermolysis bullosa of the hands and feet inherited in an autosomal dominant pattern. Treatment with adrenosteroid depressed bulla formation, but recurrence occurred with the end of therapy. An enormous pedigree with many affected persons was reported from West Virginia by Cartledge and Myers (1943). The affected persons were descendants of one Zachariah Piles, born in 1762. The blistering occurred only on the hands and feet, and mainly in warm weather after unusual walking or labor with hand tools. Friction-induced blisters in the Weber-Cockayne type of EBS are temperature-dependent. Lesions can be prevented by cooling the skin with ice before friction (Pearson, 1967). This is thus an example in man of a temperature-sensitive mutant.
In affected members of 2 unrelated families with Weber-Cockayne EBS, Chan et al. (1993) identified a heterozygous mutation in the K5 gene (I161S; 148040.0003). Ehrlich et al. (1995) identified the I161S mutation in 6 of 13 cases of ... In affected members of 2 unrelated families with Weber-Cockayne EBS, Chan et al. (1993) identified a heterozygous mutation in the K5 gene (I161S; 148040.0003). Ehrlich et al. (1995) identified the I161S mutation in 6 of 13 cases of the Weber-Cockayne type of EB simplex. The high frequency of this mutation suggested either a hotspot or founder effect. Chan et al. (1994) identified mutations in the K5 gene (148040.0004; 148040.0005) in patients with Weber-Cockayne EBS. In a family with at least 16 affected individuals in 5 generations with Weber-Cockayne type EBS, Chen et al. (1993) identified a heterozygous mutation in the KRT14 gene (148066.0005). Pfendner et al. (2005) identified a heterozygous KRT5 mutation (I161S; 148040.0003) in a patient with blistering of the hands and feet. The patient's affected mother carried the same mutation. 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. In a 49-year-old woman with mild blistering of hands and feet from birth, dystrophy of the nails with onychogryposis, and enamel hypoplasia, Jonkman et al. (2002) identified a heterozygous 2-bp deletion in the ITGB4 gene (147557.0013). She had no alopecia and no history of pyloric atresia. Electron microscopy and antigen mapping of a skin blister revealed that the level of separation was intraepidermal, low in the basal keratinocytes through the attachment plaque of the hemidesmosome. Immunofluorescence microscopy revealed absent binding of monoclonal antibody 450-11 A against the third fibronectin III repeat on the intracellular domain of integrin beta-4, whereas binding was reduced with monoclonal antibodies recognizing epitopes on amino-terminal and carboxy-terminal ends of the polypeptide. The patient was also expected to be heterozygous for a null allele, as no full-size protein was detected in vitro and the epitope 450-11 A was absent in vivo. These data showed that deletion of the third fibronectin type III repeat in the cytoplasmic domain of integrin beta-4, which is thought to interact with BP180/type XVII collagen (113811), is clinically pathogenic and results in a mild phenotype with predominant features of epidermolysis bullosa simplex.