Desmosomal Proteins and Their Role in Epidermolysis Bullosa

Epidermolysis bullosa (EB) is traditionally considered as a group of inherited skin fragility disorders in which there are genetic defects in hemidesmosome anchoring complexes. Over the last few years, however, the clinicopathological spectrum of EB has been expanded to also include primary abnormalities in desmosome junctions. Desmosomes are intercellular junctions that contribute to cell-cell adhesion, signalling, development and differentiation in various tissues, including the skin. Composed of a network of transmembranous and intracellular plaque proteins, pathogenic mutations have been reported in ten different desmosomal genes, resulting in variable phenotypes affecting the skin, hair and heart. Of these disorders, three are included in the current classification of EB: Plakophilin-1, desmoplakin and plakoglobin. It is possible that future classifications of EB will be expanded to include additional desmosomal genodermatoses in which there is also skin fragility and erosions.