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Recessive X-linked ichthyosis

Recessive X-linked ichthyosis
Author:
Jennifer L Hand, MD
Section Editor:
Moise L Levy, MD
Deputy Editor:
Rosamaria Corona, MD, DSc
Literature review current through: Jul 2022. | This topic last updated: Jul 22, 2022.

INTRODUCTION — Recessive X-linked ichthyosis (XLI; MIM #308100), also called steroid sulfatase (STS) deficiency, is an X-linked recessive ichthyosis caused by deletions or pathogenic variants in the STS gene, encoding the STS enzyme, that is generally considered nonsyndromic [1]. Due to location of the STS gene within a small region of the X chromosome that escapes X-inactivation (lyonization), recessive XLI affects almost exclusively males.

The disease presents at birth or in early infancy with dry skin and a tendency to form scales on the extremities and trunk. Along with ichthyosis vulgaris, the phenotype of XLI tends to be milder than most other hereditary forms of ichthyosis.

This topic will review the clinical features, diagnosis, and management of XLI. An overview of syndromic and nonsyndromic ichthyoses (table 1) is presented separately. (See "Overview and classification of the inherited ichthyoses".)

EPIDEMIOLOGY — Recessive XLI is the second most frequent ichthyosis after ichthyosis vulgaris. It is reported worldwide in all ethnic groups and affects almost exclusively males. XLI incidence ranges from 1 in 1300 to 1 in 9000 male births [2-5].

Since the incidence of steroid sulfatase (STS) deficiency detected by routine prenatal biochemical screening is approximately 1 in 1500 males and the rate detected by clinical diagnosis is significantly lower (1 in 3000 to 1 in 6000), STS deficiency is suspected to not cause clinically identifiable disease in a significant number of cases [6].

PATHOGENESIS — The majority of cases of recessive XLI are caused by complete deletion of the steroid sulfatase gene (STS) on chromosome Xp22.3 [7,8]. Other cases result from partial deletion or point mutations of STS [9,10]. Pathogenic deletions or variants of the STS gene cause complete loss of steroid sulfatase (STS) enzyme activity. Affected males usually inherit the X chromosome bearing a deleted or mutated gene from their carrier mother, who is clinically unaffected. Rare de novo cases have been reported [11,12]. In 5 to 8 percent of cases, a larger deletion includes additional genes adjacent to STS, resulting in a number of contiguous gene syndromes depending on the size of the deletion [13,14]. (See 'Contiguous gene syndromes' below.)

STS is a 65 kDa microsomal enzyme that localizes to the endoplasmic reticulum, Golgi apparatus, and endosomal membranes, including coated pits of placenta and several other tissues. STS hydrolyzes alkyl steroid sulfates (eg, dehydroepiandrosterone sulfate [DHEAS], aryl steroid sulfates) to their unconjugated (unsulfated) forms [15,16]. In the epidermis, the STS activity is high in the granular layer and persists in the stratum corneum, where it contributes to the production of cholesterol available to form the extracellular lamellar bilayers and participates in the regulation of permeability barrier function and desquamation. Deficient STS activity leads to accumulation of cholesterol sulfate in the stratum corneum, which inhibits proteases that normally degrade corneodesmosomes [17]. Impaired desquamation is associated with increased corneocyte cohesion, retention hyperkeratosis, and impaired skin permeability [15,18-20].

In women pregnant with an affected fetus, placental STS deficiency causes low maternal urinary and blood unconjugated estriol levels, due to inadequate deconjugation of DHEAS, which is necessary for estrogen synthesis [15]. Normally, the STS enzyme synthesizes estriol in the placenta, which circulates in maternal blood. When a fetus is affected with XLI (STS deficiency), the mother, correspondingly, has abnormally low levels of unconjugated serum estriol (uE3) during pregnancy. If a mother carrying an XLI-affected fetus is offered and pursues a second-trimester screening test for Down syndrome (see "Laboratory issues related to maternal serum screening for Down syndrome"), which relies on levels of serum analytes including uE3, the screen will be abnormal and not useful for detection of Down syndrome.

STS is expressed in the brain both during development and during normal function [6]. Several studies support that impaired STS function may affect neurodevelopment and brain function [6,17,21]. Neurocognitive differences present in affected males, who carry pathogenic point mutations and small deletions, as well as those with deletions of the entire STS gene and a small number of surrounding genes, which supports that behavioral changes are caused by reduced STS activity itself, rather than deletion of adjacent genes as previously suspected [17]. Affected males have an increased tendency toward behaviors such as inattention, impulsivity, mood concerns, and autism-related traits [6]. Data suggests that due to reduced STS activity and expression, female carriers also have an increased risk of attention deficit hyperactivity disorder (ADHD)-related behaviors but not to the same degree as affected males [6].

Atrial fibrillation is reported at an increased rate in adult males with XLI [22]. The mechanism is not known with certainty, though a relationship with circulating DHEAS levels is suspected.

PATHOLOGY — The histologic features of recessive XLI may be nonspecific, with a wide range of changes in the stratum corneum and granular layer reported. For example, the stratum corneum may appear normal or have thick hyperkeratosis (picture 1) [1]. The granular layer may appear normal (picture 2) [23], diminished [15], or absent (picture 3) [23]. In contrast with early reports of a normal to slightly thickened granular layer in recessive XLI, a review of slides from eight patients found that the granular layer was generally normal or thinned [24].

CLINICAL MANIFESTATIONS — In addition to ichthyosis, steroid sulfatase (STS) deficiency may be associated with several extracutaneous manifestations, including corneal opacities, cryptorchidism, and, less commonly, neurologic, cognitive, and developmental abnormalities [1,25,26]. Increased risk of atrial fibrillation/flutter has been reported in affected adult males [22].

Cutaneous features — The age at presentation is variable. The cutaneous features of recessive XLI may appear at birth [27] or in the first few weeks of life with mild, diffuse scaling (picture 4A-D) and develop gradually over the following months. A presentation with a collodion membrane at birth ("collodion baby") is unusual in XLI, and most parents/caregivers do not describe noticeable skin scale or dryness at birth.

Over time, the mild desquamation may be replaced by larger polygonal translucent scales (picture 5A-B) [28]. The scales may become platelike and adherent with a brownish color and particularly involve the anterior aspect of the lower extremities. Lack of involvement in flexural areas, such as the popliteal (picture 6) and antecubital (picture 7) fossae, has traditionally been considered a distinctive feature of XLI. However, in a series of 30 patients with XLI, one-third had flexural involvement [17]. Palms, soles, and the central face are often spared. During childhood, the scalp, preauricular areas, and neck may be involved ("dirty neck" appearance) [29].

The scales tend to increase throughout childhood and then stabilize after adolescence with little subsequent change. In some patients, a concurrent ichthyosis vulgaris and/or atopic dermatitis may exacerbate the symptoms [30-32]. (See 'Differential diagnosis' below.)

Pruritus is generally less severe than in other forms of ichthyosis [17,33]. The desquamation improves during the summer months and is worsened by dry and cold weather [29]. Correspondingly, pruritus is more likely in a cold environment compared with a hot environment [33]. Hypohidrosis is associated with many forms of ichthyosis and has been reported in 19 percent of patients with XLI [17].

Clinically affected individuals with XLI have an increased risk of having associated atopic dermatitis. A Spanish study identified atopic dermatitis as a comorbidity in 23 percent of XLI-affected individuals [21]. Individuals who also have mutations in the filaggrin gene, a risk factor for atopic dermatitis, may have a more severe presentation of XLI and more skin infections [17].

Extracutaneous features

Ocular — Harmless "punctate corneal opacities" are the most characteristic eye finding, present in up to 50 percent of affected males and 25 percent of carrier females [34]. The appearance is described as fine, hazy or "flour-like" comma-shaped dots in the cornea, anterior to Descemet's membrane, best visualized using a slit lamp (picture 8) [30]. In vivo confocal microscopy has also been reported to be useful for visualization [35]. These punctate corneal opacities are usually asymptomatic and only rarely can cause recurrent corneal erosions [1,34].

Genitourinary — Cryptorchidism is described in up to 20 percent of affected boys [1]. A Spanish study of 30 patients found 10 percent of affected boys required orchiopexy. Despite cryptorchidism, affected males have normal sexual development, testosterone levels, and fertility [1]. Of particular concern to patients and families is a possible association of recessive XLI with testicular germ cell cancer independent of cryptorchidism. However, the data to support this association are weak, with only a few cases reported in the literature [36,37]. (See "Undescended testes (cryptorchidism) in children: Management".)

There are a few case reports of nephrotic syndrome associated with recessive XLI [38-41]. However, a true association has not been proven.

Cardiac — In a large UK Biobank study of males aged 40 to 69 years, atrial fibrillation or flutter was reported in 10.5 percent of STS deletion carriers compared with a rate of 2.7 percent in controls [22].

Cognitive and behavioral — Boys with recessive XLI have a higher rate of cognitive and behavioral disorders, especially attention deficit hyperactivity disorder (ADHD), compared with nonaffected individuals in the same age range [17,27]. In a study of 25 boys with recessive XLI, 10 fulfilled the criteria for ADHD, especially the inattentive subtype, and five of the criteria for an autistic-spectrum disorder or related language/communication difficulty [25]. In another study of patients from 25 families, 30 percent were affected with ADHD. Despite this well-supported association of XLI and ADHD, a study revealed no difference in highest academic level achieved between STS deletion carriers (male or female) aged 40 to 69 years and controls [22]. (See "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis", section on 'Clinical features' and "Autism spectrum disorder: Clinical features".)

Epilepsy risk may also be associated. Epilepsy was overrepresented (13 percent) in a group of 30 clinically diagnosed male children in Spain [17]. Increased seizure risk in XLI is further supported in a report of three affected male children with self-limited focal epilepsy of childhood and an Xp22.31 STS deletion that includes STS, PUDP, and MIR4767. These authors propose that STS pathogenic variants are an independent risk factor for seizures [42].

Contiguous gene syndromes — Abnormal recombination of homologous sequences in the STS chromosomal region may cause terminal or interstitial deletions that include adjacent genes, resulting in complicated clinical phenotypes [43]. In addition to ichthyosis, abnormalities reported in male patients with recessive XLI and contiguous gene syndromes include:

Cognitive disability [44,45]

Hypogonadotropic hypogonadism and anosmia (Kallmann syndrome, MIM #308700), caused by a large deletion of the short arm of the X chromosome proximal to and including the STS gene [46] (see "Isolated gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)")

Chondrodysplasia punctata, nasal hypoplasia, and developmental delay [47-49]

Developmental delay and short stature [50]

Anosmia, hypogonadotropic hypogonadism, nystagmus, and decreased visual acuity [51]

PERINATAL MANIFESTATIONS OF STEROID SULFATASE DEFICIENCY — Steroid sulfatase (STS) is a key enzyme in the biosynthesis of estriol in the human placenta. A placental STS deficiency, which occurs in pregnancies of XLI fetuses, causes abnormally low levels of serum estriol in mothers during pregnancy. Recessive XLI may be diagnosed prenatally as an incidental finding in pregnant women undergoing a screening blood test for Down syndrome, which includes alpha-fetoprotein (AFP), unconjugated estriol, human chorionic gonadotropin, and inhibin A. (See "Down syndrome: Overview of prenatal screening".)

The impact of STS deficiency on pregnancy and delivery is unclear. Some authors report a delayed or prolonged labor (>20 hours) and reduced response to oxytocin, especially in primiparous females [28,52]. However, no special interventions are recommended, unless there are specific obstetric indications [52,53].

DIAGNOSIS

Clinical suspicion — The diagnosis of recessive XLI is suspected in an infant based upon one or more of the following [1]:

Presence of unusually dry skin in the first weeks of life that evolves to polygonal, brownish scales

Birth history characterized by a prolonged (>20 hours) labor and/or nonelective cesarean section

Maternal finding of low serum estriol in the second trimester of pregnancy

Family history of scaly skin affecting the male relatives of the mother

The diagnosis of recessive XLI can be confirmed by biochemical techniques demonstrating absent steroid sulfatase (STS) enzyme activity or by molecular techniques demonstrating a deletion or mutation of the STS gene.

Biochemical diagnosis — The demonstration of reduced STS activity in cultured fibroblasts has the highest sensitivity because it detects cases caused by chromosomal deletions as well as those caused by mutations. Fibroblasts can be cultured from skin biopsy using a standard technique. Typically, a 4 mm punch biopsy from a convenient area of the skin (such as under the upper arm) is placed in a sterile container with standard culture media (not formalin) and sent to a laboratory that performs fibroblast culture. A request for STS enzyme activity testing should accompany the specimen.

Molecular diagnosis — The diagnosis of recessive XLI can be confirmed by chromosomal microarray (CMA) test of peripheral blood. Using CMA, the STS region of the X chromosome (Xp22.3) can be examined for a microdeletion. However, CMA cannot detect the minority of recessive XLI cases caused by point mutations in STS or very small deletions. (See "Tools for genetics and genomics: Cytogenetics and molecular genetics", section on 'Fluorescence in situ hybridization'.)

In suspected cases in which CMA is negative for an STS deletion, DNA sequencing for point mutations in STS and small deletions can be performed. CMA is a powerful genetic test that interrogates the entire genome for small deletions and copy number variants. CMA is used in obstetrics for certain situations such as fetal congenital anomalies, and in the postnatal setting in children with multiple congenital anomalies not explained by a specific syndrome. (See "Prenatal diagnosis of chromosomal imbalance: Chromosomal microarray".)

CMA may detect recessive XLI prenatally and is also useful to exclude an associated contiguous gene syndrome. Similarly, in patients who present with suspected XLI and congenital anomalies, CMA and genetic consultation may be helpful for accurate diagnosis.

Prenatal diagnosis — Since the mothers of XLI-affected fetuses have abnormally low levels of serum estriol during pregnancy, the diagnosis is sometimes made prenatally in women who undergo a screening blood test for Down syndrome in the second trimester of pregnancy, which includes the measurement of unconjugated estriol. (See 'Perinatal manifestations of steroid sulfatase deficiency' above.)

When the diagnosis of STS deficiency is made prenatally, further evaluation to exclude a contiguous gene syndrome using CMA is recommended [13]. (See 'Molecular diagnosis' above.)

Carrier detection — Measurement of STS enzyme activity in fibroblast culture is not useful to detect carrier females. If an affected male is identified using CMA, DNA sequencing, or fluorescence in situ hybridization (FISH) testing (see 'Molecular diagnosis' above), then female relatives (eg, the mother) can be tested for carrier status using the same technique in a targeted fashion. Genetic consultation is useful for families to understand the testing strategy and implications of the findings.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of XLI includes:

Ichthyosis vulgaris – In contrast to recessive XLI, the skin is likely to lack the translucent, polygonal scale of recessive XLI in infants and children with ichthyosis vulgaris. Palmar hyperlinearity is characteristic of ichthyosis vulgaris, but is usually absent in XLI (picture 9) [17]. On histology, the granular layer is absent in ichthyosis vulgaris but is usually normal or thinned in XLI. (See "Overview and classification of the inherited ichthyoses", section on 'Ichthyosis vulgaris'.)

Lamellar ichthyosis and congenital ichthyosiform erythroderma – Lamellar ichthyosis is more severe than XLI and typically presents at birth with a collodion membrane (picture 10) and later with large, plate-like scales that are most prominent on the trunk and lower extremities (picture 11). (See "Overview and classification of the inherited ichthyoses", section on 'Lamellar ichthyosis and congenital ichthyosiform erythroderma'.)

Atopic dermatitis – In infants and young children, atopic dermatitis typically presents with dry skin, pruritus, and red, scaly, or weeping lesions on the extensor surfaces and cheeks or scalp (picture 12A-C). Histology shows spongiosis (epidermal edema) and a lymphohistiocytic infiltrate in the dermis. In contrast to atopic dermatitis, XLI is not associated with inflammation, vesiculation, or pruritus. However, atopic dermatitis may rarely be present concurrently with XLI. Individuals with recessive XLI have heightened risk of atopic dermatitis, and the two conditions may occur together. (See "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis".)

MANAGEMENT

General considerations — There is no definitive cure for recessive XLI. The disease rarely interferes with the activities of daily living and individuals with mild forms may not require treatment [1]. However, some patients with XLI experience a significantly reduced quality of life, due to self-consciousness and social embarrassment [54-56]. These patients may need lifelong treatment to control scaling and skin dryness and improve their skin appearance.

Education of parents/caregivers and patients about the importance of daily bathing and regular, frequent application of emollients is an essential part of the management of XLI. It is also essential to guide the patient in the choice of cosmetically acceptable creams and lotions to improve his/her compliance to treatment [57]. An excellent resource for patients and parents/caregivers with information on skin care can be found on the website of the Foundation for Ichthyosis and Related Skin Types (FIRST).

Overheating — In some individuals, the skin is dry and thick enough to impede normal function of the sweat glands by mechanically blocking them. These patients may have a tendency to become overheated, especially in direct sunlight [1]. One of the first signs of overheating is increased redness of the skin. Ready access to a cool environment or water, if needed, is recommended.

Affected individuals usually learn over time what they can or cannot tolerate, and overheating rarely causes medical problems.

Control of scaling and dryness — Treatment of recessive XLI is directed at removing scales, reducing skin dryness, and improving skin appearance without causing excessive irritation. It involves regular bathing and use of emollients and keratolytics. Patients with severe disease may benefit from intermittent use of topical or systemic retinoids. (See "Inherited ichthyosis: Overview of management".)

Daily bathtub soaks in water or long showers with gentle removal of scale using a roughly textured sponge are helpful. Addition of baking soda or lubricating bath oils to bath water may be helpful [58]. Moisturizing creams or ointments should be applied immediately after bathing, while the skin is still damp. Useful moisturizers typically contain oils alone (eg, petroleum jelly) or in combination with humectants (eg, sodium lactate, low-concentration urea, propylene glycol).

Infants and young children — In neonates with XLI, maintaining skin hydration with environmental humidity and bland emollients is usually sufficient to remove the thin scales and prevent their formation. In infants and young children, daily baths followed by the application of emollients is usually sufficient to remove scales. The application of topical keratolytics should be avoided because of the high risk of toxicity due to systemic absorption [59-61].

Older children and adults — Patients with thick scales and markedly increased stratum corneum thickness benefit from creams or ointments containing one or more keratolytic agents such as alpha-hydroxyacids (lactic acid and glycolic acid), salicylic acid, urea at high concentration, and propylene glycol.

Keratolytic preparations available on the market usually contain 5 to 12% lactic acid, 2 to 10% urea, 5 to 15% glycolic acid, 10 to 25% propylene glycol, or 3 to 6% salicylic acid. An excessive concentration of keratolytic agents may cause skin irritation, pain, and excess peeling. As a general rule, concentration of keratolytic creams may be increased in a "start low, go slow," stepwise fashion to avoid burning and irritation. Patients with unsatisfactory response to single keratolytics may benefit from using ointments containing a combination of keratolytics, such as 5% lactic acid with 10% urea or 2% salicylic acid with 20% urea.

Evidence on the efficacy of keratolytics for the treatment of ichthyosis is limited to a few low-quality randomized trials and observational studies, and their use is mainly based upon clinical experience and patient preference. In one study, 60 children with mild to moderate types of ichthyosis treated one side of the most severely affected extremity with a 10% urea cream and the contralateral side with vehicle for eight weeks [62]. A very good or good investigator-assessed improvement was noted in more areas treated with 10% urea lotion than those treated with vehicle (79 versus 62 percent).

Patients with severe X-linked ichthyosis — Adult patients with more severe forms of XLI may benefit of intermittent courses of topical retinoids (eg, tazarotene) or oral retinoids (eg, isotretinoin, acitretin) [63]. Retinoids have anti-keratinizing properties and modulate keratinocyte proliferation and differentiation. An alternative to topical or systemic retinoids are retinoic acid metabolism-blocking agents such as liarozole and rambazole. Liarozole has received the orphan drug status by the United States Federal Drug Administration and the European Medicines Agency for the treatment of congenital ichthyosis, but it is not yet available on the market.

Evidence on the efficacy of topical or systemic retinoids in XLI is limited to a few small uncontrolled studies and single-case reports and one randomized trial [64-67]. However, their use is supported by evidence of efficacy in other types of severe congenital ichthyoses and by clinical experience:

In one right-left comparison study, 12 patients with congenital ichthyosis (4 with XLI) applied tazarotene 0.05% gel on a skin area ≤10 percent of the body surface area and an ointment containing 10% urea on the contralateral area twice daily for two weeks and then twice weekly for two additional weeks [64]. In the four patients with recessive XLI, a marked clinical improvement was noted only on the side treated with tazarotene after 14 to 20 days, and the beneficial effect persisted for up to two months after discontinuing tazarotene. Adverse effects of tazarotene were mild irritation and discomfort that did not require the interruption of treatment.

In a small right-left comparison trial, liarozole 5% cream was more effective than vehicle in reducing scaling and roughness in 12 patients with recessive XLI, epidermolytic ichthyosis, or lamellar ichthyosis [66].

In a randomized trial including 32 patients (21 with XLI), oral liarozole 150 mg per day was as effective as oral acitretin 35 mg per day in inducing a marked improvement in scaling and erythema, as assessed by clinician evaluation and patient self-evaluation [67]. Adverse events were moderate and less frequent in the liarozole group.

The use of topical retinoids is limited because of concern for systemic absorption due to application on large body areas for long periods of time. However, the transepidermal absorption of tazarotene appears to be negligible. In a small study including nine children with ichthyosis (four with XLI), patients applied 0.05% or 0.1% tazarotene cream or gel on 20 to 90 percent of the body area for one month to two years [68]. The blood levels of tazarotene were measured 12 to 25 hours after the last application. Of nine patients, seven had undetectable levels of tazarotene or tazarotenic acid, and two had levels <0.3 ng/mL.

Adverse effects of systemic retinoids include mucosal dryness, photosensitivity, hyperlipidemia, transaminase elevation, and skeletal hyperostosis. Because recessive XLI only affects males, the risk of teratogenicity associated with systemic retinoids is not a concern.

Management of extracutaneous manifestations — Patients with extracutaneous manifestations and patients with contiguous gene syndromes may require a specialized or multidisciplinary approach:

The corneal punctate opacities in XLI are asymptomatic and generally do not cause harm. A baseline ophthalmology exam using a slit lamp to examine the cornea can be considered at baseline to document the presence or absence of corneal changes associated with XLI.

The management of cryptorchidism is discussed elsewhere (see "Undescended testes (cryptorchidism) in children: Clinical features and evaluation"). Of particular concern to patients and families is a possible association of XLI with testicular germ cell cancer [36,69]. The data to support a true connection are weak [15]. Because the evidence for a true association of XLI with testicular cancer is weak outside the setting of cryptorchidism, no additional screening measures are recommended for patients without a history of cryptorchidism. (See "Epidemiology of and risk factors for testicular germ cell tumors".)

The management of children with contiguous gene syndromes who present with developmental, endocrine, or neurologic abnormalities and/or intellectual disability requires a multidisciplinary team, including a pediatrician, a pediatric neurologist, a geneticist, and occupational and physical therapists.

Genetic counseling — Patients diagnosed with recessive XLI may benefit from genetics consultation to better understand the inheritance pattern and impact on family members. Mothers who are carriers of steroid sulfatase (STS) deficiency will pass the X chromosome bearing the STS deletion or mutation to 50 percent of offspring. Therefore, 50 percent of sons will be affected by recessive XLI and 50 percent of daughters will be carriers (figure 1). Affected fathers will never transmit the disease to their sons, but all daughters will be carriers. (See "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)", section on 'Sex-linked'.)

Rare affected females are usually associated with homozygous mutations on both X chromosomes due to consanguinity [70].

PROGNOSIS AND FOLLOW-UP — In the absence of a contiguous gene syndrome, the prognosis for patients affected with recessive XLI is excellent. Some authors advocate for a multispecialty approach in assessment of children with XLI to include assessment for the presence of neuropsychiatric signs [27]. There is no known reduction in life expectancy associated with XLI [1]. For patients with severe skin dryness and scaling, scheduled dermatologic follow-up (eg, every six weeks) is recommended until the skin dryness is improved and well managed by the patient and/or family. In milder cases, "as needed" periodic follow-up is usually sufficient.

ONLINE RESOURCES — Information and support for patients and families with recessive XLI can be found on the website of the Foundation for Ichthyosis and Related Skin Types (FIRST).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ichthyosis".)

SUMMARY AND RECOMMENDATIONS

Definition and pathogenesis – Recessive X-linked ichthyosis (XLI; MIM #308100), also called steroid sulfatase (STS) deficiency, is an X-linked recessive, nonsyndromic ichthyosis caused by deletions or mutations in the STS gene, encoding the STS enzyme. (See 'Introduction' above and 'Pathogenesis' above.)

Cutaneous features – The cutaneous features of recessive XLI may appear in the first few weeks of life with mild, diffuse scaling (picture 4A-D) and develop gradually over the following months. Over time, the mild desquamation may be replaced by large polygonal, brownish scales that involve particularly the anterior aspect of the lower extremities (picture 5A-B). The flexural areas tend to be spared. (See 'Cutaneous features' above.)

Extracutaneous features – Extracutaneous features include asymptomatic punctate corneal opacities and cryptorchidism. Deletions of the STS genes and adjacent genes result in complicated clinical phenotypes called contiguous gene syndromes. (See 'Extracutaneous features' above and 'Contiguous gene syndromes' above.)

Diagnosis – The diagnosis of recessive XLI can be confirmed by biochemical techniques demonstrating absent STS enzyme activity in cultured fibroblasts or by molecular techniques demonstrating a deletion or point mutation of the STS gene. Chromosomal microarray (CMA) may be used to exclude an associated contiguous gene syndrome. (See 'Diagnosis' above.)

Management – There is no definitive cure for recessive XLI. Treatment is directed at removing scales, reducing skin dryness, and improving skin appearance without causing excessive irritation. It involves regular bathing and use of emollients and keratolytics. Patients with severe disease may benefit from intermittent use of topical or systemic retinoids. (See 'Management' above.)

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Topic 15472 Version 16.0

References