Research into the molecular genetics and pathomechanisms of
ichthyoses have advanced considerably, resulting in the identification of several causative genes and molecules underlying the disease. In 2009, the First
Ichthyosis Consensus Conference was held to establish a consensus for the nomenclature and classification of inherited
ichthyoses, by which an international consensus for the classification of inherited
ichthyosis was achieved. In this review, the pathogeneses of various
ichthyoses are summarized based on their revised classification and terminology. Skin barrier defects are involved in the pathogenesis of various types of
ichthyosis. The known causative molecules underlying
ichthyosis include ABCA12,
lipoxygenase-3, 12R-lipoxygenase, CYP4F22, ichthyin and
steroid sulfatase, all of which are thought to be related to the intercellular
lipid layers. ABCA12 is a known keratinocyte
lipid transporter associated with
lipid transport in lamellar granules and a loss of ABCA12 function leads to defective
lipid transport in the keratinocytes, resulting in the most severe,
harlequin ichthyosis phenotype. Other causative molecules for
ichthyoses are
transglutaminase 1,
keratins and
filaggrin.
Transglutaminase 1 plays a role in cornified cell envelope formation.
Keratins 1, 10 and 2 are involved in the
keratin network of suprabasal keratinocytes and
filaggrin is essential for the formation of
keratohyalin granules. It is important to obtain information concerning genetic defects and to elucidate ichthyotic disease pathomechanisms for the establishment of an effective
therapy and beneficial genetic counseling, including a prenatal diagnosis for families affected by ichthyotic disease.