Darter’s disease is an autosomal dominant acantholytic disorder (OMIM # 124200) characterized by a peculiar keratinization of the epidermis, nails, and mucous membranes, resulting in a persistent eruption of keratotic papules predominantly in seborrheic areas (upper and central trunk, flexures, scalp and forehead), palmar pits and nail dystrophy. Involvement may be severe, with widespread itchy malodorous crusted plaques, painful erosions, blistering, and mucosal lesions. Secondary infection is common. Sun, heat, and sweating exacerbate the disease, which never remits (even though oral retinoids may reduce hyperkeratosis). Neuropsychiatric abnormalities including mild mental retardation, epilepsy, and schizophrenia have been reported in some families (Burge and Wilkinson 1992, Jacobsen et al. 1999): whether this association is due to pleiotropism of the mutated gene or reflects coincidence is not clear (OMIM 2006). Several variants have been described (see below).