The role of abnormalities in the distal pathway of cholesterol synthesis in the Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD) syndrome.

[child syndrome]

CHILD syndrome (Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects ) is a rare X-linked dominant ichthyotic disorder . CHILD syndrome results from loss of function mutations in the NSDHL gene , which leads to inhibition of cholesterol synthesis and accumulation of toxic metabolic intermediates in affected tissues . The CHILD syndrome skin is characterized by plaques topped by waxy scales and a variety of developmental defects in extracutaneous tissues , particularly limb hypoplasia or aplasia . Strikingly , these alterations are commonly segregated to either the right or left side of the body midline with little to no manifestations on the ipsilateral side . By understanding the underlying disease mechanism of CHILD syndrome , a pathogenesis-based therapy has been developed that successfully reverses the CHILD syndrome skin phenotype and has potential applications to the treatment of other ichthyoses . This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier . Guest Editors : Kenneth R . Feingold and Peter Elias .