Introduction:
X-linked ichthyosis is a hereditary disorder that occurs due to a mutation in the enzyme steroid sulfatase or STS. This enzyme is responsible for cholesterol sulfate metabolism, which is necessary for the proper development of the stratum corneum (upper layer of skin). In patients with the disorder, the absence of the enzyme leads to the development of hyperkeratosis and improper skin barrier.
Ichthyosis means the appearance of thick, flaky dry skin. The term is derived from the Greek word 'ichthys', which means fish. The skin of a person suffering from it needs to be constantly moisturized. X-linked ichthyosis occurs due to the mutation of the STS enzyme and is one of the most common types of ichthyosis and human enzyme deficiency diseases. Therefore, it is also known as STS deficiency and was first recognized by Dr. Wells and Kerr.
What Causes Recessive X-linked Ichthyosis?
This occurs due to the mutation of the enzyme STS. The deficiency leads to improper metabolism of cholesterol sulfate, which accumulates in the stratum corneum (outer layer of skin). This leads to an improper skin barrier and the retention of cells of the stratum corneum (called corneocytes), which gives rise to the scaling appearance of the skin. The deficiency of the STS enzyme inhibits the metabolism of cholesterol sulfate, which causes it to accumulate on the surface of the skin, which leads to:
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Corneocyte accumulation.
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Hyperkeratosis- thickening of the outer layer of skin.
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Impaired skin barrier function.
Genetic Cause:
The STS gene coding is linked to the X chromosome. 90 % of patients will have a complete deletion of this gene, and ten percent will have a point or partial deletion of the gene.
Sometimes this gene deletion can cause deletions in neighboring genes also, which could result in conditions such as:
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Mental retardation.
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Short stature.
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X-linked chondrodysplasia punctata: it is a disorder that affects the cartilage and bones that is seen as spots or stippling on the ends of bones, usually affecting males.
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Kallmann syndrome: it is a disease that causes hypogonadism and leads to the impairment of smell and lack of development of sexual features.
Who Is Affected by X-linked Ichthyosis?
It is categorized as recessive, not expressed if an individual has a normal STS gene. In such a case, the disease is not expressed.
Males have more predilection for inheriting the disorder than females. Since it is X-linked, if a faulty chromosome is passed on, the condition is expressed in men, whereas the females will only be carriers. Females have two X chromosomes, while men have one X-chromosome. An affected male can pass his defective chromosome; his sons will be affected, while his daughters will only be carriers. Men have only one X chromosome; if that is faulty, they will be affected, whereas in women, since they have two pairs of the X chromosome, even if one is faulty, the disease will not be expressed. This is the reason that men have more predilection for the disease.
Roughly one in 6000 males are affected. There is no pronounced racial or geographical linkage. The cases are rare in females, as it is expressed if both sides of the family are affected.
What Does X-linked Ichthyosis Look Like?
The skin of the person with the condition will be very dry. It is characterized by scaling of the skin in a rhomboid, light gray, or dark brown appearance. It is seen at the back of the neck, extensor surface of hands and legs, and upper trunk. The skin becomes dry and accumulates polygonal scales. The condition is noticed at birth or within the first six months.
Clinical Features Include the Following:
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The prominent feature of the condition is scaling.
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The scaling is more evident on the extensor surface of limbs, the side of the trunk.
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It is uniformly and symmetrically distributed.
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The face is usually spared, except in the area in front of the ear.
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Scales resemble fish scales.
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The scalp may be affected but tend to disappear during childhood.
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Hair, nails, palms, and soles are generally not affected.
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It aggravates during winter and reduces in summer.
Features other than dermal manifestations include:
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Pregnant mothers who carry affected children may suffer from prolonged labor due to low placental STS.
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Corneal opacities.
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Undescended testicles- cryptorchidism. This condition is found more in men with X-linked ichthyosis than in the unaffected public.
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Neurological abnormalities include epilepsy and reduced ability to smell (hyposmia).
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There is an increased risk of testicular cancer. But that is not due to undescended testicles.
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Mental retardation.
Non-skin manifestations and other systemic conditions occur when the neighboring genes are also affected by the deletion.
How Is It Diagnosed?
History, especially family history and clinical features, is the primary basis of diagnosis.
Biochemical Analysis: Tests such as serum protein electrophoresis and ST's activity assay may be done. Skin cells - fibroblasts and keratinocytes are biochemically analyzed.
Genetic Analysis: It includes,
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Southern blot.
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PCR- A polymerase chain reaction.
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FISH- Fluorescent in situ hybridization.
Prenatal Analysis: It includes,
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Reduced estrogen levels in pregnancy.
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Genetic testing of amniotic fluid if there is a family history.
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Presence of non-hydrolyzed sulfate steroids in the urine of the mother.
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Genetic testing may miss X-linked ichthyosis if it is caused by point mutations; however, the most reliable method of diagnosis is genetic analysis.
A skin biopsy may not be sufficient in confirming the disease as epidermal findings such as hyperkeratosis and hypergranulosis may not be enough. It is differentiated from ichthyosis vulgaris by the scaling of the skin on the abdomen.
What Is the Treatment?
There is no definitive treatment; the treatment is aimed at improving the scaling of the skin and overall appearance.
Physical therapy may be beneficial in some, such as:
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Exfoliation: With a pumice or exfoliating sponge, remove the scales.
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Moisturizer: Topical emollients, when applied after a bath, are effective in keeping the skin moisturized.
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Keratolytics: Agents containing salicylic acid, glycolic acid, and urea will help improve the appearance of the skin, as they help with desquamation. Some agents, such as:
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Calcipotriol ointment.
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Topical Isotretinoin.
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Topical Tazarotene is effective.
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- Genetic counseling may be offered to parents with a family history of the condition.
- Gene transfer and its effectiveness are still under research.
Conclusion:
X-linked ichthyosis is a condition that is chronic in nature and will persist through adult life. But with proper care, scaling can be reduced, and it is not a condition that threatens life expectancy. Being a genetic disorder that is X-linked, it affects the male population more and is characterized by a scaly appearance on the skin due to the absence of the STS enzyme. Women are usually unaffected but can pass it to their sons if they are carriers. Proper care and topical agents can significantly improve the appearance of the skin.
