Epidemiology, medical genetics, diagnosis and treatment of harlequin ichthyosis in Japan

Ichthyoses are a group of disorders marked by whitish, brown or dark-brown scales on the skin of almost the whole body. Harlequin ichthyosis (HI) is the most severe form. Neonatal death from HI was once common. Due to intensive neonatal care and, probably, to the early introduction of oral retinoids, HI outcome has improved. For definitive diagnosis and the exclusion of other disorders, such as lamellar ichthyosis, which also shows a collodion baby phenotype, it is helpful to refer to electron microscopy of abnormal or absent lamellar granules and a heavy accumulation of lipid droplets in the keratinocytes. ATP-binding cassette transporter A12 (ABCA12) is known as the causative gene of HI. Severe ABCA12 deficiency results in malformation of intercellular lipid layers in the cornified layers and leads to epidermal lipid barrier disruption. In HI patients, at least one mutation on each allele must be a truncation or deletion mutation to cause serious loss of ABCA12 function. Identification of the gene underlying HI has enabled DNA-based prenatal diagnosis for HI at the earlier stages of pregnancy with low risk. There are no curative treatments for HI. Abca12-deficient mice were created as a model of HI. Treatment of the model mice with retinoid or steroid has not been successful.