X-Linked Ichthyosis
X-linked ichthyosis (XLI) is an inherited condition that causes dry, scaly skin in males. It is also called steroid sulfatase deficiency (STSD). Most people with this condition have mild skin problems, but it varies from person to person. This is a lifelong condition, but the dry skin may improve over time. Life expectancy is normal.
There are many different types of inherited skin conditions. X-linked ichthyosis is milder than most other types. A person with XLI will not suddenly change to have a different type of ichthyosis.
Most parents do not report any obvious skin changes at birth. Babies with XLI often start to have dry skin and mild scaling in the first few weeks of life. This can develop into brownish scaly areas on the skin over the following months. About 1 in 5 boys with this condition will also have undescended testicles at birth.
It is estimated that one in every 1,500 newborn boys has XLI. It is less common in people of African descent. In many people, the skin changes may not be recognized and diagnosed as XLI.
Individuals with XLI have absent or low levels of an enzyme called steroid sulfatase. This enzyme is important for helping the body shed skin cells. The gene that makes this enzyme is called the STS gene. This gene is deleted (missing) in most people with XLI, so there is usually no STS enzyme being made in the body. Without the STS enzyme, skin cells build up in scaly patches.
The inheritance of XLI depends on a person's sex chromosomes, typically XX for females and XY for males. XLI is called an X-linked condition because the gene that causes XLI is found on the X chromosome. Most females have two copies of the STS gene and males only have one. That means males will have XLI if their only STS gene is deleted or not working. A female who has one STS gene that is deleted or not working is a silent carrier. There is a second copy of the gene that works normally, so she is not affected. A female (XX) carrier has a 1 in 2 (50%) chance in any pregnancy for a male (XY) child to inherit the condition. There is also a 1 in 2 (50%) chance for a female (XX) child to be a silent carrier. If a male (XY) has XLI, none of his sons (XY) will inherit the condition and all of his daughters (XX) will be carriers.
A small number of people with XLI also have other genes deleted near the STS gene. This can lead to medical concerns beyond skin changes, depending on which genes are involved.
The diagnosis may be suspected when a person has skin changes commonly seen in XLI. The diagnosis is confirmed by measuring the amount of STS enzyme in the blood or testing the STS gene.
XLI may be identified during pregnancy if a pregnant person has a screening test called quad screening or AFP4. This screening test is not offered in all pregnancies. XLI causes undetectable or very low levels of a substance called “estriol”, which often leads to a screening result that needs follow-up. A diagnosis of XLI can be confirmed by taking a sample from the developing baby, either by CVS or amniocentesis during pregnancy, or by testing the baby after birth. Special testing is ordered to look for differences in the STS gene or measure the STS enzyme.
Birth defects are not part of XLI. If a prenatal ultrasound finds birth defects in the baby, it could be a sign that other genes may be involved. A diagnostic test would be needed to find out.
The condition rarely interferes with daily life and mild forms may not require treatment. Daily bathing and regular use of lotion can help improve the skin. Medicated lotion may be used in older children and adults to reduce symptoms.
National Organization of Rare Diseases (NORD): X-Linked Ichthyosis - General information about XLI.
Foundation for Ichthyosis and Related Skin Types (FIRST): X-Linked Ichthyosis - Information about XLI from a parent and family support organization for skin conditions.
Last reviewed: November 2022
Reviewed by: Kimberly Barr, LCGC, KP NCAL Regional Genetics