What is X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)?
X-linked ichthyosis is a skin disorder that is inherited, which means it happens because of a mutation or change in a specific gene. Specifically, this gene is known as STS, which is responsible for producing an enzyme called steroid sulfatase. When the STS gene undergoes mutation or deletion, the body cannot produce this enzyme, leading to the skin disorder.
Although it can affect anyone in the world regardless of race or ethnicity, it is generally more common in men than women. That’s why it’s often referred to as “X-linked,” indicating that it’s related to the X chromosome that men carry. In fact, it’s one of the most common types of a group of skin conditions called ichthyosis.
Doctors became aware of this particular form of ichthyosis in 1965, and we now know that between 15% to 20% of people with the condition start showing symptoms at birth or shortly thereafter. With this condition, the skin cells are produced normally, but they don’t shed as they should. As a result, the skin becomes dry and scaly.
In the beginning, the symptoms are usually mild, but over time, they can develop into large, polygonal, brownish scales. Other features of this condition can include changes in the cornea of the eye (asymptomatic punctate corneal opacities), undescended testicles in males (cryptorchidism), and sometimes cognitive or behavioral problems like attention-deficit hyperactivity disorder (ADHD).
The missing enzyme leads to high levels of a substance called cholesterol sulfate and low levels of regular cholesterol, disrupting the normal function of the skin. Interestingly, the scaling usually does not affect flexibility or mobile areas of the skin, like the inner elbows or knees, palms, soles, hair, and nails. Additionally, the front side of the lower legs is typically the most affected area.
Unfortunately, there is currently no complete cure for this condition, but effective treatments are available to manage symptoms. The primary aim of treatment is to alleviate skin dryness, reduce the formation of scales, and improve the appearance of the skin without causing irritation.
What Causes X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)?
X-linked ichthyosis is a skin condition causing a scaly skin appearance and is mainly caused by the total loss of a gene called STS, which is located on a specific part of the X-chromosome (Xp22.31). In some cases, partial loss or small changes in this gene can also lead to the disease.
It’s interesting that women who carry the mutated STS gene don’t show any signs of the disease. This is because the specific region on the X-chromosome where the STS gene is located doesn’t get switched off during a process called X-inactivation. This process happens only in females to prevent an overactivity of the X-chromosome genes.
Sometimes, the disease can occur from a new mutation in the STS gene that wasn’t inherited from the parents. About 8% of the affected individuals may even have changes in genes close to the STS gene, which can lead to different genetic syndromes depending on what the variation is.
A small group of patients might have a variant in a gene called filaggrin (FLG), which can result in a more severe form of the disease and increase their chances of developing a skin condition called atopic dermatitis.
Risk Factors and Frequency for X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)
X-linked ichthyosis comes second to ichthyosis vulgaris as the most common type of ichthyosis. This skin condition can affect anyone, regardless of race or ethnic group. However, it is mainly seen in males (hence its name), with rates ranging from 1 in 2,500 to 1 in 6,000 males. Interestingly, there have been a few cases reported in females, who got the disease from their parents.
- X-linked ichthyosis is the second most common type of ichthyosis, with the most common being ichthyosis vulgaris.
- It affects all ethnic groups and races equally.
- The condition is predominantly seen in males, not females.
- The incidence in males ranges from 1 in 2,500 to 1 in 6,000.
- There have been rare cases reported in females who inherited it from their carrier mothers and affected fathers.
Signs and Symptoms of X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)
X-Linked Ichthyosis is a medical condition where symptoms could begin at any time. The symptoms are initially mild for about 15% to 20% of patients either at birth or in the weeks afterward. The condition starts with small amounts of scaling that eventually become larger, clearer scales as the individual grows from a child to a teen. It’s not common for patients with this condition to exhibit a shiny, tight layer of skin at birth (known as a collodion membrane).
Typically, the scaling appears on the front of the lower legs but usually doesn’t affect the nails, palms, soles of the feet, or areas of the body where the skin folds onto itself, like the back of the knees and inside of elbows. However, about one third of patients with X-Linked Ichthyosis show symptoms in these areas. This condition can also affect the scalp, areas in front of the ears, and the neck, causing what is known as a “dirty neck” appearance.
Patients with this condition may not have itchy skin, or the itching is less severe than other types of Ichthyosis. Peeling skin is usually mild during the summer but can worsen during cold, dry weather. Additional physical symptoms include:
- Reduced sweating (seen in 19% of patients)
- Atopic dermatitis or eczema (seen in 23% of patients)
- White spots on the cornea (seen in 50% of affected males and 25% of female carriers)
- The undescended testicle(s) (seen in 20% of affected patients)
- Irregular heart beat occurring between ages 40 and 69 (seen in 10.5% of affected males)
- ADHD and other cognitive or behavioral disorders (seen in 30% of affected patients)
- Seizures
No significant evidence suggests that this condition affects sexual development, testosterone levels, or fertility. However, female carriers of this condition can also display white spots on the cornea and have an increased risk of ADHD.
There are also other potential conditions related to variations in the genetic make-up of patients with X-linked Ichthyosis. These are known as contiguous gene syndromes and can show up as combinations of Ichthyosis and other conditions, including:
- Cognitive disabilities
- Hypogonadotropic hypogonadism and anosmia, or Kallmann syndrome (due to a large deletion in the STS gene)
- Chondrodysplasia punctata, which includes stippling near the ends of bones, developmental delays, and short stature
- Nystagmus (uncontrolled eye movement) and decreased visual acuity
Testing for X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)
If you or a loved one are suspected to have X-linked ichthyosis, a skin condition that causes dry, scaly skin, certain signs could indicate this. First, a baby born with unusually dry skin that develops into brownish scales with geometric shapes within the first few weeks of life. Second, a labor that lasts for over 20 hours, or an unplanned C-section. If there are men on your mother’s side who have scaly skin, it could be a hereditary sign. Low levels of a hormone called estriol in the mother’s blood during the middle of pregnancy could also be a clue.
Getting a diagnosis for X-linked ichthyosis usually involves biochemical and genetic tests. Doctors can test the activity of a particular enzyme (steroid synthase) in skin cells, which helps to identify the condition whether caused by missing genes or gene mutations. A blood test can provide further confirmation by identifying whether certain sections of chromosomes are missing or duplicated.
However, this type of blood test can’t pick up on small gene mutations or deletions. In this case, a more detailed gene test known as DNA sequencing is available. This test uses a method called fluorescence in situ hybridization (FISH), which allows doctors to see your genes under a microscope.
Certain tools such as chromosomal microarray can exclude the possibility of related genetic conditions. For recognizing carriers of the disease, techniques such as multiple number PCR (QF-PCR) and FISH can identify whether the STS gene, linked to ichthyosis, is completely deleted. In prenatal diagnosis of X-linked ichthyosis, chromosomal microarray can be especially helpful in spotting the presence of related genetic conditions.
Treatment Options for X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)
As of now, there’s no cure-all solution for X-linked ichthyosis, a rare skin condition. That said, if the disease isn’t severe, you may not need treatment. But, if it’s causing discomfort or affecting your quality of life, there are steps you can take to manage symptoms. These aim to lessen skin dryness, reduce flaky skin, and improve your skin’s appearance through daily bathing, regular use of moisturizers, and applying agents meant to loosen and remove dead and dry skin layers.
Taking long showers/baths and carefully removing any skin flaky or scales with a textured sponge can be helpful. Make a habit of applying moisturizers based on petrolatum (like Vaseline) or humectants (that draw in water) like sodium lactate, urea, or propylene glycol to your damp skin. You can get extra benefits by adding baking soda or oils to your bath.
For older children and adults, the treatment plan might include keratolytics, which are products designed to break down the keratin in your dead and dry skin cells. However, these can irritate the skin, so they might not be the best fit for young kids. If you’re using these on children, be sure to apply them cautiously, especially over large areas, to avoid the risk of too much being absorbed into the body and causing side effects. Keratolytics usually contain ingredients like lactic acid, urea, glycolic acid, propylene glycol, or salicylic acid.
Keratolytics can be applied to the areas with affected skin once or twice a day. Start slowly, applying a little bit to an area once a week to avoid irritating the skin, then gradually increase how much you use. If your skin isn’t improving, you can try a combination of treatments, such as lactic acid with urea or salicylic acid with urea.
For people with more severe forms of X-linked ichthyosis, treatment might involve the occasional use of stronger medications called retinoids, which can be applied to your skin or taken orally. However, research into the effectiveness of these treatments is limited. That said, there is some evidence that a gel called tazarotene can lead to significant improvements, and an oral drug called acitretin might effectively lessen scaling and redness.
If you have X-linked ichthyosis, you generally won’t need an eye exam because most people with this skin disorder don’t have symptoms involving their eyes. However, if you have undescended testes (cryptorchidism), it’s a good idea to see a urologist and get regular check-ups for testicular cancer. The link between testicular cancer and X-linked ichthyosis isn’t clear, but a few cases have been reported.
The skin thickening that occurs in X-linked ichthyosis might block your sweat glands, making it hard for you to control your body temperature. Red skin is an early sign of overheating, so stay cool and hydrated if this happens to you. Children with a group of specific genetic disorders linked to X-linked ichthyosis should be cared for by a diverse group of medical professionals who can address their symptoms as needed.
What else can X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency) be?
When a patient presents with X-linked ichthyosis, a condition characterized by dry, scaly skin, doctors need to consider other conditions with similar symptoms. These include:
- Ichthyosis vulgaris
- Lamellar ichthyosis and congenital ichthyosiform erythroderma
- Atopic dermatitis
- Congenital ichthyosiform erythroderma
- Harlequin ichthyosis
- Epidermolytic ichthyosis
- Sjögren-Larsson syndrome
- Anhidrotic ectodermal dysplasia
- CHILD syndrome (Congenital hemidysplasia with ichthyosiform erythroderma and limb defects)
- Conradi-Hünermann-Happle syndrome or Chondrodysplasia punctata type 2
- Netherton syndrome
- Trichothiodystrophy
- Multiple sulfatase deficiency
- Refsum disease
- Keratitis-ichthyosis-deafness syndrome
- Neutral lipid storage disease
- Ichthyosis prematurity syndrome
Moreover, acquired ichthyosis, where dry, scaly skin develops later in life, is often associated with certain diseases. These include:
- Hodgkin lymphomas
- Anaplastic large-cell lymphoma or lymphomatoid papulosis
- Leiomyosarcoma
- Multiple myeloma
- Cutaneous T-cell lymphoma
- Kaposi sarcoma
- Breast, lung, or bladder carcinoma
- Graft versus host disease
Doctors can often tell the difference between congenital (from birth) and acquired ichthyosis because scaling skin in acquired ichthyosis may also be present on the palms, soles, and folds of the skin. The suspected reasons for this are that the tumor secretes substances that stimulate skin cell growth or there is a response of the immune system attacking the skin.
What to expect with X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)
People without a contiguous gene syndrome generally live an average lifespan. However, their quality of life can differ greatly depending on how serious their symptoms are. More severe symptoms may make a person feel more discomfort and lower their self-esteem. Interestingly, some people might actually see their symptoms improve as they age, with less severe symptoms in adulthood than what they experienced in childhood.
Healthcare professionals must not ignore the emotional and social effects of having a skin condition that others can see. Getting the necessary support from skin specialists, genetic counselors, and psychologists can be helpful for dealing with both the medical and emotional aspects of the condition. With the right management, many people with X-linked ichthyosis, a type of skin condition, can lead fulfilling lives. Early diagnosis, proper medical attention, and a supportive healthcare team are critical for a positive outcome.
Possible Complications When Diagnosed with X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)
X-linked ichthyosis is a condition that mainly affects the skin but can lead to other complications. Here are some possible complications and related factors that could affect a patient with X-linked ichthyosis:
- Skin infections: The dry, scale-like skin seen in X-linked ichthyosis patients can make them more prone to bacterial or fungal skin infections. These can cause discomfort, redness, swelling, and pain.
- Pruritus or itching: This condition can cause the skin to become itchy. Constant scratching can damage the skin and increase the chances of an infection.
- Atopic dermatitis: Some patients with X-linked ichthyosis may also have atopic dermatitis. This can cause the skin to become itchy, red, and inflamed.
- Keratosis pilaris: This condition causes small, hard, and often red or white bumps on the skin, especially on the arms and thighs. It can occur with X-linked ichthyosis, complicating the texture and appearance of the skin.
- Retinoid dermatitis: Sometimes, retinoids can irritate the skin and cause redness.
- Psychosocial complications: The visible skin conditions can lead to psychological and social challenges, such as low self-esteem, depression, and social isolation.
- Heat intolerance: The dry, thickened skin may make regulating body temperature difficult and increase the chance of becoming overheated in hot and humid conditions.
- Prolonged labor and cesarean section: The lack of the sulfatase enzyme in the placenta may cause issues in starting or progressing labor.
- Cryptorchidism: This condition in children can increase the risk of groin hernias, testicular twisting, testicular injury, reduced fertility, and testicular cancer.
- Testicular germ cell tumors: There are a few cases that suggest a link between testicular germ cell tumors and X-linked ichthyosis, but the exact connection is still unclear.
- Atrial fibrillation and atrial flutter: These heart conditions can become more common in men between the ages of 40 and 69.
- Cognitive and behavioral disorders: Conditions like mood disorders, ADHD, anxiety, and depression are more prevalent in males with X-linked ichthyosis and carrier females compared to the general population.
Preventing X-Linked Ichthyosis (Steroid Sulfatase (STS) Deficiency)
People with X-linked ichthyosis should understand that even though their skin cells are made normally, they shed at a slower rate. To avoid problems, it’s important to follow a careful skincare routine. This not only makes the skin look better, but also helps to avoid skin infections, reduce itchiness, and keep the body at the proper temperature. Moreover, it’s important not to injure the skin for the best management of this condition.
It’s just as important for patients, caregivers, and families to understand this condition. X-linked ichthyosis has a genetic factor, and a meeting with a genetics specialist could help to understand how it’s passed down in families, and how it might affect other family members. It’s also essential that patients and caregivers know that this condition is lifelong and that, as of now, there’s no cure for it. Healthcare professionals should be ready to handle the medical and emotional aspects of this disease.
By helping patients understand the condition, stick to their treatment plans, and make informed choices, healthcare providers can give individuals with X-linked ichthyosis the power to manage their symptoms and improve their lives. A good online resource for patients, caregivers, loved ones, and families is The Foundation for Ichthyosis and Related Skin Types. You can find them at: https://www.firstskinfoundation.org/