The pathogenesis of severe congenital ichthyosis of the neonate

Severe congenital ichthyosis of the neonate include several major subtypes, i.e. harlequin ichthyosis, lamellar ichthyosis (LI), and congenital ichthyosiform erythroderma. Knowledge of the pathogenetic mechanisms is significant for the precise diagnosis, treatment, genetic counseling and prenatal diagnosis. This article reviews recent advances in studies on genetic defects and pathogenetic mechanisms of these severe congenital ichthyosis and, in addition, discuss the feasibility and methods of their prenatal diagnosis. Recently, reduced activity of the serine/threonine protein phosphatase in keratinocytes was suggested to be the cause of harlequin ichthyosis. In some families of LI, transglutaminase 1 gene mutations were identified as causative genetic defects and transglutaminase 1 is thought to be one of the candidate molecules for non-bullous congenital ichthyosiform erythroderma (NBCIE). Genotype/phenotype correlation in bullous congenital ichthyosis is now being clarified. Mutations within the rod domain, not in the beginning or the end of the rod domain, of keratin 10 were reported in annular epidermolytic ichthyosis (AEI), the distinct subtype of bullous congenital ichthyosiform erythroderma.