Hereditary diseases of desmosomes

Desmosomes are key adhesion complexes in most epithelia, including epidermis. Although structural components of desmosomes have been identified as target antigens in several of the autoimmune blistering skin diseases, there are relatively few data on inherited disorders arising from mutations in genes encoding these proteins and glycoproteins. For example, an association between an inherited abnormality of desmosomes and Darier disease and Hailey Hailey disease has been proposed on histopathological grounds, but genetic linkage studies have not invoked known desmosomal gene loci. However, linkage analyses have implicated one or more of the desmosomal cadherins (desmogleins 1-3, desmocollins 1-3), the genes for which are tightly clustered within a 650-kb region on 18q12.1, in the pathogenesis of a different autosomal dominant genodermatosis, striate palmoplantar keratoderma. In addition, a rare autosomal recessive skin fragility-ectodermal dysplasia syndrome has recently been recognised which results from total ablation of plakophilin 1, an intracellular desmosomal plaque protein that reinforces adhesion between the cytoskeleton and the cell membrane in terminally differentiating keratinocytes. In the future, it is likely that a number of other desmosome genodermatoses will be identified, each resulting from dominant or recessively inherited mutations in component structural proteins.