ABSTRACT:
Harlequin ichthyosis is an extremely rare and historically lethal congenital disorder of the skin caused by abnormal keratinization. There are serious implications for the family to consider: the high risk that their newborn will die soon, as well as future family planning issues. Linked to deletion and truncation mutations of a keratinocyte lipid transporter, HI is characterized by diffuse epidermal hyperkeratinization and defective desquamation. At birth, the HI phenotype is striking with thick hyperkeratotic plate-like scales with deep dermal fissures, severe ectropion and eclabium. Over the first months of life, the hyperkeratotic covering is shed, revealing a diffusely erythematous, scaly epidermis, which persists for the remainder of the patient's life. Although HI infants have historically succumbed in the perinatal period related to their profound epidermal compromise, the prognosis of HI infants has vastly improved over the past 20 years. Research into the molecular genetics and pathomechanisms of ichthyoses has advanced considerably, resulting in the identification of several causative genes and molecules underlying the disease. In this review, the pathogeneses of various ichthyoses are summarized based on their revised classification and terminology. 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. This article reviews the embryology and currently understood pathophysiology of the disease, as well as current methods used to diagnose and treat these infants.