- Darier's disease is an autosomal dominant disorder resulting in abnormally keratinizing epidermis. The gene has been localized to the long arm of chromosome 12. Research has eliminated candidate genes such as keratins, desmosomal proteins, retinoid receptors, and transglutaminases. The epidermal characteristics of the disease have been reproduced by the use of skin equivalents in tissue culture and establish that the abnormal gene is intrinsic to the epidermis. There are suggestions that hyperkeratosis and signs of premature cell death are the result of intracellular maturation and clefting and cell separation suggest cell surface or cell membrane or possibly signal transduction related abnormalities. Both mechanical trauma and sunlight may precipitate the lesions of Darier's disease and offer insights potentially about the role between environment and the epidermal response. The histopathologic findings of Darier's disease are found with other epidermal diseases, and since cells may be more susceptible to apoptosis and more resistant to the effects of retinoids, the findings have applicability to a broad range of neoplastic and inflammatory skin diseases. Defining Darier's disease at the genetic and physiologic levels may lead to better understanding of the mechanisms of epidermal changes and lead to new therapeutic modalities.
