Last Updated: 2023-10-12
Author(s): Lindemann H.
Csorsz, 1928; Orel,1929; Wells and Kerr, 1965
X-linked recessive ichthyosis; X-linked recessive ichthyosis; Recessive ichthyosis vulgaris; Sex-linked ichthyosis vulgaris; Ichthyosis serpentina; Ichthyosis vulgaris; Steroid sulphatase deficiency; Wells-Kerr type; Wells-Kerr ichthyosis; Xerodermia; XRI
It is an X-linked recessive inherited cornification disorder caused by a gene defect on the short arm of the X chromosome in the steroid sulphatase gene (STS gene; Xp22.3). Due to the pattern of inheritance, the male sex is almost exclusively affected. Coarse, firmly adhering scales appear as early as birth or in infancy. The course of the skin changes can be progressive until puberty.
It is a globally occurring, not too rare skin disease. Incidence: 1:2000-6000. Prevalence is estimated at 1:4000.
By extending the gene mutation to neighbouring genes, X-linked ichthyosis can occur in combination with various syndromes and disease associations.
Possible associations are with Kallmann syndrome, Refsum syndrome, epidermolysis bullosa dystrophica, hypergonadotropic hypogonadism, oculocutaneous albinism type 1, autism, ADHD or cryptorchidism.
In 90 % of cases, X-linked ichthyosis is a deletion of the STS gene. There is a deficit of microsomal steroid sulphatase. This is an enzyme that cleaves steroid sulphates from cholesterol sulphate, among others, by hydrolysis. This leads to an increased cholesterol sulphate concentration in the epidermis. This inhibits the epidermal serine protease, resulting in a reduced desquamation of the corneocytes. This leads to a lack of exfoliation of the skin cells and excessive keratinisation (retention hyperkeratosis)
Typically, the first skin changes in X-linked ichthyosis can be noticed shortly after birth or in infancy (2-6 months). However, these can be variable. Subtle, superficial or fulminant scaling with erythroderma may occur. Subtle skin changes in particular may disappear within weeks and flare up again later in life as clearly recognisable ichthyosis.
In X-linked ichthyosis, there are usually coarse firmly adherent scales on the extremities and trunk. With age, the scaling may turn grey. The neck is almost always affected. The flexor sides may or may not show scaling. There is typically no hyperlinearity on the hands and feet.
Testicular undescendancy may be observed in 1 in 5 affected individuals.
Punctate asymptomatic corneal opacities may be observed.
The diagnosis is usually made via the clinic. Human genetic analyses can confirm the diagnosis. Laboratory diagnosis of X-linked ichthyosis can be made by blood sampling to determine the activity of the enzyme steroid sulphatase. Accumulation of cholesterol sulphate can be detected in serum lipoprotein electrophoresis, chromatography or spectrophotometry using skin flakes, placental tissue or amniotic fluid. If the family history is positive, prenatal diagnostics via chorionic villus sampling or amniocentesis are available. A non-invasive prenatal diagnosis can be made by a lowered oestrogen level in the serum or maternal urine.
The disease manifests itself especially on the extensor sides of the extremities. There may also be ichthyotic skin changes on the abdomen, ears, capillitium and lower trunk.
Occasionally, the bends of the knees may also be affected, while the armpits and crooks of the elbows often remain free.
Hyperkeratosis or parakeratosis may be seen with a slightly thickened stratum granulosum. Electron microscopy shows an increase in keratohyaline granules. A large number of melanosomes may be found in the stratum corneum.
With age, there may be a slight improvement in X-linked ichthyosis. It is a benign form of ichthyosis with normal life expectancy.
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