Acantholytic Genodermatoses

Acantholysis is the main pathology of Darier disease and Hailey Hailey disease which are mainly autosomal dominant. Darier disease is due to mutation in the ATP2A2 gene, encoding sarco/endoplasmic reticulum ATPase type 2 (SERCA2) responsible for calcium transport in the endoplasmic reticulum of epidermal cells. Its malfunction causes aberrant keratinization and acantholysis. However, Hailey Hailey disease is due to a mutated gene, ATP2C1, leading to changes in calcium transport into the Golgi apparatus that result in desmosomal dysfunction and keratinocyte acantholysis.