Ichthyosis includes a number of subtypes from congenital severe forms, such as
harlequin ichthyosis (HI), to mild non-congenital forms, such as
ichthyosis vulgaris. Recently, research into the pathomechanisms of
ichthyoses has dramatically advanced and led to the identification of several causative genes and molecules underlying the genetic defects. In most types of
ichthyosis, pathogenic mechanisms are associated with defects in skin barrier function. Three major components of the stratum corneum barrier are (i) intercellular
lipid layers, (ii) cornified cell envelope and (iii)
keratin-
filaggrin degradation products. The causative molecules underlying
ichthyosis subtypes include ABCA12,
lipoxygenase-3, 12R-lipoxygenase, CYP4F2 homolog, ichthyin and
steroid sulphatase and all these are thought to be related to the intercellular
lipid layers.
Transglutaminase 1 has a function in cornified cell envelope formation.
Keratins 1, 10 and 2 are involved in the
keratin network of suprabasal keratinocytes and
filaggrin are essential for formation of
keratohyalin granules. In fact, loss of ABCA12 function leads to a defective
lipid barrier in the stratum corneum, resulting in the HI phenotype and ABCA12 is a known keratinocyte
lipid transporter associated with
lipid transport in lamellar granules.
Filaggrin gene mutations in
ichthyosis vulgaris cause
keratohyalin granule deficiency. Information concerning genetic defects and ichthyotic disease pathomechanisms are beneficial to develop effective
therapy and provide information for genetic counselling including prenatal diagnosis for families affected by ichthyotic disease.