Jouni Uitto, Leila Youssefian, Amir Hossein Saeidian, Hassan Vahidnezhad
DOI: 10.2340/00015555-3431

The heritable forms of keratinization disorders, including various forms of ichthyosis and keratodermas, comprise a phenotypically heterogeneous group of diseases which can be divided into syndromic and non-syndromic forms. In the non-syndromic forms, the clinical manifestations are limited to the cutaneous structures while the syndromic ones are associated with a spectrum of extracutaneous manifestations. The inheritance in different families can be autosomal dominant, autosomal recessive or either X-linked dominant or recessive. Currently at least 67 distinct genes have been associated with different forms of ichthyosis. These genes can be grouped on the basis of their physiological involvement, including genes encoding structural components of epidermis, those involved in epidermal lipid metabolism, or those critical for cell-cell adhesion, and keratinocyte differentiation. This overview highlights some of the recent progress made in understanding the molecular genetics of keratinization disorders, and presents selected, recently characterized cases as representative of different forms of heritable ichthyosis.

Patients with ichthyosis manifest with dry and scaly skin, with considerable phenotypic variability. The heritable forms of ichthyosis are associated with mutations in over 60 different genes which encode proteins critical for normal physiological function of the skin. This overview highlights some of the new findings in the genetics of heritable forms of ichthyosis and emphasizes the connection of skin findings to extracutaneous manifestations, in some forms of the syndromic ichthyosis. The presentation also emphasizes the importance of determining the specific mutations in the underlying genes, which allows subclassification of the patients into distinct categories, with the capability to prognosticate the severity and the overall outcome of the disease in general terms. The knowledge of mutations in specific genes is also required for application of allele-specific therapies being developed for this group of disorders currently without specific treatments.