X-linked ichthyosis is an X-linked disorder caused due to the deficiency of the enzyme - steroid sulfatase, which leads to the build-up of cholesterol sulfate in the skin. This causes the skin cells to attach to each other more strongly than usual with reduced exfoliation and building up of the skin cells in clumps which give rise to the scales-like appearance of the skin.
X-linked ichthyosis (XLI) is an inherited disorder caused by the deficiency of the steroid sulfatase (STS) enzyme which maintains the integrity of the skin. Deficiency of this enzyme leads to accumulation of cholesterol sulfate in the cutaneous cells which adhere to each other strongly and do not exfoliate. Instead, they clump together leading to the classical appearance of scaly skin. Although this condition is more commonly seen amongst men (X-linked), a few cases in heterozygous females (carriers) with corneal opacities has also been reported .
Typically XLI starts at birth  or in the neonatal period with some atypical cases presenting either later  in childhood or with fewer phenotypic features. Classically the infant has scales on the posterior aspect of the neck, trunk, extensor aspects of the limbs  and scalp. With the progression of the disease in childhood, prominent scalp scaling extending to the preauricular region, posterior neck and involving the flexural aspects of the limbs is noted. Usually, the palms and the soles are unaffected.The scales are adherent, brown, polygonal and described as "dirty". They are more prominent in winter and cold weather and may present initially as erythroderma . Hair and nails are normal in patients with XLI. Corneal opacities have been reported in affected males  as well as a late manifestation in heterozygous carriers . Cryptorchidism and testicular cancer cases have also been reported   in XLI patients.
Atypical presentations with milder phenotypic manifestations like dermatitis  or lower limb scaling alone  can also occur. Rarer clinical features include hypertrophic pyloric stenosis  , short stature, and mental retardation.
Diagnosis of XLI is based on the appearance of the classical scaly pattern of the skin in affected individuals. A complete family history and physical examination are important before proceeding with confirmatory tests. Slit-lamp examination in affected adult males and heterozygous females   is likely to show comma-shaped corneal opacities in the posterior capsule and corneal stroma  .
Diagnosis of XLI can be confirmed postnatally with genetic analysis of STS activity assays of placental cells, cutaneous fibroblasts, keratinocytes, or lymphocytes. Biochemical testing will confirm the deficiency of arylsulfatase C. Antenatally, XLI can be diagnosed with fluorescence in situ hybridization (FISH) . Genetic diagnosis of homozygotic XLI can be done with Polymerase chain reaction and Southern blot testing while multiplex quantitative fluorescent polymerase chain reaction (PCR), as well as, FISH are required to identify carriers and complete deletions .
Although skin samples in mild cases may appear normal on histology, samples obtained from more severe cases show eosinophilic hyperkeratosis, with rete ridges, and a sparse infiltrate of perivascular and periappendageal lymphocytes and histiocytes.