X-linked ichthyosis: an update

Abstract

X-linked ichthyosis is a genetic disorder of keratinization characterized by a generalized desquamation of large, adherent, dark brown scales. Extracutaneous manifestations include corneal opacity and cryptorchidism. Since 1978 it has been known that a deficit in steroid sulphatase enzyme (STS) is responsible for the abnormal cutaneous scaling, although the exact physiological mechanism remains uncertain. The STS gene has been mapped to the distal part of the short arm of the X chromosome. Interestingly, this region escapes X chromosome inactivation and has the highest ratio of chromosomal deletions among all genetic disorders, complete deletions having been found in up to 90% of patients. Diagnosis of patients with X-linked ichthyosis and female carriers is based on biochemical and genetic analysis. The latter currently seems to be the most accurate method in the majority of cases.

Genetic analysis of a 12-year-old boy with X-linked ichthyosis in association with sclerosing glomerulonephritis

“…STS is a membrane-bound microsomal enzyme, ubiquitously expressed in mammalian tissues, that hydrolyzes various 3 β-hydroxysteroid sulfates (4,25). The enzyme is crucial in the conversion of sulfated steroid precursors to estrogens during human pregnancies and in the desulfation of cholesterol sulfate, an important step in skin metabolism.…”

“…The skin lesions persist throughout the life of the patient. Extracutaneous manifestations are common, particularly with corneal opacities and cryptorchidism (4). Other associated features, although extremely rare, include mental retardation, epilepsy, pyloric hypertrophy, congenital defects of the abdominal wall and acute lymphoblastic leukemia (3,5).…”

“…The remaining 10% of males demonstrate a point mutation or partial deletion (4,6,7). Larger deletions involving neighboring genes (contiguous gene deletion syndromes) may result in XLI associated with Kallman syndrome (KS) or X-linked recessive chondrodysplasia punctata (CDXP) (4,6,7).…”

“…It affects ~1:2,000-6,000 males, with little racial or geographic variation (2)(3)(4). Of the males affected, >90% manifest with generalized exfoliation of the skin within a few weeks of being born.…”

The Biological Roles of Steroid Sulfonation

“…Most cases (≈80-90%) are caused by complete deletion of the STS gene, whereas small deletions or point mutations account for the remainder of cases [56]. Loss of STS leads to an accumulation (up to 20-fold increase) of its substrate, cholesterol sulfate, in plasma and red cell membranes, as well as the epidermis [57]. Excess cholesterol sulfate in the skin, delays desquamation which leads to hyperkeratosis that appears as large, polygonal, dark brown scales on the skin.…”