X-linked Ichthyosis

Table of Contents


X-linked Ichthyosis is a genetic skin disorder that primarily affects males. This condition stems from an inborn metabolic error characterized by a deficiency of the enzyme steroid sulfatase. Typically, this enzyme is responsible for metabolizing cholesterol sulfate, a member of the steroid chemical family that contributes to skin integrity. When the metabolic process of steroids is disrupted, causing an accumulation of cholesterol sulfate within skin cells, these cells become excessively adhesive. This abnormality inhibits the regular shedding of dead skin cells and results in the accumulation and clustering of skin cells into scales.

In vitro fertilization (IVF) and preimplantation genetic testing (PGT) are significant advancements in the realm of reproductive medicine and genetics, particularly for individuals at risk of transmitting genetic disorders like X-linked Ichthyosis For couples with a known risk of passing on X-linked Ichthyosis to their offspring, IVF coupled with PGT offers a proactive approach. In this process, eggs are fertilized in a lab setting, and the resulting embryos are screened for the specific genetic mutations associated with X-linked Ichthyosis This enables the selection of embryos without the disorder for implantation, significantly reducing the likelihood of the child inheriting X-linked Ichthyosis. Thus, IVF and PGT provide a powerful combination for family planning, particularly for those with a genetic predisposition to this condition, allowing them to minimize the risk of genetic transmission while achieving pregnancy.


X-linked recessive disorders are genetic conditions that are encoded on the X chromosome. In humans, females typically have two X chromosomes, while males have one X chromosome and one Y chromosome. This distinction is important because in females, the presence of a normal gene on one X chromosome can mask the expression of disease traits on the other X chromosome. However, in males who possess only one X chromosome, inheriting a gene associated with a disease on the X chromosome will lead to the manifestation of the disease. Men with X-linked disorders pass the gene to all their daughters, making them carriers, but do not transmit it to their sons. In contrast, women who are carriers of an X-linked disorder have a 50 percent chance of passing on the carrier status to their daughters and a 50 percent chance of transmitting the disease itself to their sons.

The underlying cause of the abnormal cutaneous scaling observed in X-linked Ichthyosis is a deficiency in the STS gene located on the Xp22.3 region of the X chromosome. Most individuals with X-linked Ichthyosis have extensive deletions (complete or partial) of the STS gene, although point mutations can also result in complete STS deficiency. Importantly, female carriers of the STS gene do not display any clinical manifestations because the gene resides in an X-chromosome region that is not subject to X-inactivation. In some cases, de novo STS mutations can occur.


X-linked Ichthyosis is the second most common form of ichthyosis, with ichthyosis vulgaris being the most prevalent type. This condition is found at similar rates in all ethnic groups and races worldwide. As the name implies, X-linked Ichthyosis predominantly affects males. The reported incidence of X-linked ichthyosis ranges from 1 out of 2500 to 1 out of 6000 males. While the overwhelming majority of cases occur in males, there have been a few reported instances of X-linked ichthyosis in females. These females were the offspring of fathers with the disorder and carrier mothers, and they can be carriers themselves.

There is no racial predisposition for X-linked ichthyosis. This condition typically presents at birth or during early infancy and may become more prominent as the affected individual grows older.


Boys born with X-linked ichthyosis typically appear normal at birth, but skin symptoms usually emerge within the first year of life. One of the initial signs of the disorder is the presence of brownish scales that adhere to the skin. Early on, this condition predominantly affects the back and legs, with sparing of areas such as the face, scalp, palms and soles, as well as the hollows of the elbows and knees.

Approximately half of adult males with X-linked ichthyosis may develop comma-shaped corneal opacities in their eyes, as observed during an examination by an ophthalmologist. Importantly, these opacities do not interfere with vision. Symptoms often show significant improvement in warmer months and in humid climates.

A small percentage of affected males may experience undescended testes, a condition known as cryptorchidism, which could elevate their risk of developing testicular malignancies.

In the case of women who carry the X-linked ichthyosis gene and give birth to sons affected by the disorder, there may be a delay in labor initiation or a failure to initiate labor. This is due to the enzyme defect causing a reduction in maternal estriol production during late pregnancy, potentially affecting the labor and delivery process. Low serum estriol levels detected through prenatal screening can indicate the presence of a fetus with X-linked ichthyosis.

Clinical Description

The onset of X-linked ichthyosis may occur within the first few days of life, marked by the development of generalized non-erythematous (non-red), polygonal, and loosely adherent scales. As the condition progresses, these scales transform into grayish or blackish adherent scales, which are particularly prominent on the trunk, the extensor and flexor regions of the extremities, and the neck. This latter manifestation gives rise to the characteristic “dirty-neck” appearance. Notably, skin folds, palms, and soles typically remain unaffected. Scaling tends to improve with age and is more pronounced during the summer months.

In some cases, delayed birth may be observed due to insufficient cervical dilatation in affected pregnant individuals. Additionally, X-linked ichthyosis may present with extracutaneous manifestations such as testicular maldescent, attention deficit and hyperactivity disorder (ADHD), and/or corneal opacities. In rare instances, large deletions that encompass adjacent genes may result in more complex phenotypes, leading to contiguous gene deletion syndromes like Kallman’s syndrome, the recessive form of X-linked chondrodysplasia punctata, short stature, intellectual disability, or central nervous system anomalies.

Treatment / Management

The medical management of X-linked ichthyosis primarily aims to alleviate symptoms by reducing scales, mitigating skin dryness, and improving overall skin appearance. This can be achieved through regular bathing and the application of emollients and keratolytic agents. Moisturizers containing petrolatum or humectants should be applied to damp skin for optimal effectiveness. It’s worth noting that the use of topical keratolytics should be avoided during the first six months of life and exercised cautiously in children, particularly when applied over large body surfaces, due to the potential risk of systemic absorption and associated toxicities.

In cases of severe X-linked ichthyosis, individuals may find relief from intermittent use of topical or even systemic retinoids. While there is limited substantial evidence on the efficacy of keratolytic agents, topical, and systemic retinoids in the treatment of mild to severe X-linked ichthyosis, clinical responses have been observed.

For males with X-linked ichthyosis, routine ophthalmology examinations are typically unnecessary, as the punctuate corneal opacities that may develop are asymptomatic. However, if cryptorchidism (undescended testes) is present, a consultation with a urologist is warranted. Furthermore, individuals with X-linked ichthyosis, particularly those with cryptorchidism, should undergo routine monitoring for testicular carcinoma, although this occurrence is rare and has only been reported in a single patient with no direct link to cryptorchidism.

Differential Diagnosis

  • Acrodermatitis enteropathica
  • Acute complications of sarcoidosis
  • Acute retinal necrosis
  • An ocular manifestation of HIV
  • Atopic dermatitis in emergency medicine
  • Herpes zoster
  • Interstitial keratitis
  • Ophthalmologic manifestations of leukaemia
  • Psoriasis
  • Retinitis pigmentosa

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