Ectodermal Dysplasia Skin Fragility Syndrome

Ectodermal dysplasia skin fragility (EDSF) syndrome results from loss-of-function mutations on both alleles of the PKP1 gene encoding plakophilin 1. The syndrome is also known as plakophilin 1-deficiency or epidermolysus bullosa simplex-plakophilin 1. This autosomal recessive disorder represents the first example of an inherited disorder of desmosome cell-cell junctions in humans. Loss of PKP1 expression leads to skin erosions and crusting, notably with perioral fissuring as well as palmoplantar hyperkeratosis with painful cracking of the skin. Other more variable but prototypic features of EDSF syndrome include growth delay, hypotrichosis or alopecia, and nail dystrophy. Unlike some other genetic diseases of desmosomes, there are no cardiac abnormalities. EDSF syndrome is classified as a suprabasal form of epidermolysis bullosa simplex, and thus far, there have been approximately 12 published cases. This chapter reviews the clinical, structural and molecular pathology of this desmosomal genodermatosis.