X-linked ichthyosis (abbreviated XLI) is a skin condition caused by the hereditary deficiency of the steroid sulfatase (STS) enzyme that affects 1 in 2000 to 1 in 6000 males.

[9] Heart rhythm abnormalities in individuals with XLI tend to co-occur with disorders of the gastrointestinal tract, and are likely to result from steroid sulfatase deficiency.

[2] Individuals with XLI appear at increased risk of neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder and some affected individuals exhibit mood problems [12] Mood problems in XLI appear to be most influenced by stigma or bullying associated with the skin condition, and by difficulties with treating the skin condition.

[15] Individuals with XLI can exhibit intellectual disability, although this is thought to be due to deletions encompassing neighboring genes (e.g. VCX) in addition to STS.

[16] The skin and medical conditions associated with XLI are likely to be due to perturbed basement membrane function and abnormal interactions with the extracellular matrix.

This gene partially escapes X-inactivation and females normally express higher amounts of the STS enzyme than males.

[23] For this reason, XLI most commonly affects males, although individuals with numeric abnormalities of the sex chromosomes (45,X and 47,XXY) who also carry STS deletions or mutations would be exceptions to this rule.

Due to random segregation of the chromosomes during gametogenesis, each pregnancy will be subject to the same probabilities, regardless of the number of previously affected or unaffected offspring.

The above recurrence risks are based on the assumption that an affected male or carrier female will have children with an unaffected or non-carrier individual.

[27] XLI can be suspected based on clinical findings, although symptoms can take varying amounts of time to become evident, from a few hours after birth, up to a year in milder cases.

[30] Timber Pharmaceuticals is planning on conducting a phase 3 trial of its investigational topical isotretinoin product in the second quarter of 2022 for the treatment of congential ichthyosis.