RARE DISEASE
Recessive X-linked ichthyosis
Recessive X-linked ichthyosis
Recessive X-linked ichthyosis
Synonyms: RXLI, Steroid sulfatase deficiency, X-linked ichthyosis, XLI
Synonyms: RXLI, Steroid sulfatase deficiency, X-linked ichthyosis, XLI
Synonyms: RXLI, Steroid sulfatase deficiency, X-linked ichthyosis, XLI
Drug discovery
2
drugs
With orphan designations
Overview
Recessive X-linked ichthyosis (RXLI) is an X-linked genetic disorder caused by STS gene mutations, leading to steroid sulfatase deficiency. It primarily affects males (1:2,000-6,000) with generalized dark brown/gray scales most prominent on extensor surfaces, neck, and trunk, sparing palms/soles [1][5][7]. Associated features include cryptorchidism (5-20%), asymptomatic corneal opacities (50%), and neurodevelopmental disorders like ADHD (40%) [5][7][12]. Diagnosis combines clinical findings, biochemical testing (STS activity), and genetic analysis [1][5].
Categories: rare genetic diseases, rare ophthalmic disorders, rare skin diseases
Research Papers
98 drug discovery papers about Recessive X-linked ichthyosis, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
98 drug discovery papers about Recessive X-linked ichthyosis, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-02-26 | Steroid Sulfatase Deficiency: Clinical Manifestations and Psychological Aspects in Light of Current Evidence.
Syndromic epidermal differentiation disorder associated with steroid sulfatase deficiency (STS-sEDD) is a hereditary disorder of keratinization caused by mutations or deletions in the STS gene. Although historically classified as a dermatological condition, accumulating evidence indicates that STS-sEDD represents a multisystem disorder with significant neuropsychological, endocrine, and cardiological involvement. Psychosocial consequences substantially increase disease burden, highlighting the need for integrated and multidisciplinary care. The aim of this paper is to summarize current knowledge on the biological, clinical, neuropsychological, and psychosocial aspects of STS-sEDD and to identify gaps and challenges in contemporary clinical practice. A purposive, non-systematic review of Polish- and English-language literature published between 1960 and 2025 was conducted. The analysis included articles retrieved from PubMed, Scopus, and Google Scholar databases, as well as materials produced by patient advocacy organizations. Literature selection was carried out in two stages (abstract and full-text review) by two independent reviewers, using keyword sets related to genetic, clinical, neurodevelopmental, and psychosocial domains. Available data indicate that approximately 85-90% of STS-sEDD cases result from complete deletion of the STS gene. Larger deletions within the Xp22.3 region lead to contiguous gene syndromes and are associated with additional manifestations, including attention-deficit/hyperactivity disorder, autism spectrum disorder, endocrine abnormalities, and cardiac arrhythmias. Clinically, STS-sEDD is characterized by typical cutaneous findings accompanied by subtle cognitive and neurodevelopmental deficits, which may also be observed in female carriers. Beyond its medical features, STS-sEDD is associated with stigmatization, reduced quality of life, and significant emotional distress affecting both patients and their families. Evidence suggests that therapeutic education and structured psychological support improve daily functioning and coping. STS-sEDD should therefore be recognized as a multisystem condition requiring early diagnosis and coordinated, interdisciplinary management. The implementation of comprehensive care models has the potential to substantially improve outcomes and quality of life for affected individuals.
2026-01-15 | Early Neonatal presentation of X-linked Ichthyosis – A case report
X-linked ichthyosis (XLI) is an inherited disorder of keratinisation caused by a deficiency of the enzyme steroid sulfatase (STS), leading to accumulation of cholesterol sulfate in the stratum corneum and resulting in retention hyperkeratosis. Affected males typically present in the neonatal period with dark brown, polygonal scales over the trunk, neck, and extensor surfaces, with relative sparing of flexures, face, palms, and soles. Extracutaneous manifestations such as cryptorchidism or corneal opacities may be seen, and larger STS deletions can be associated with neurodevelopmental features. We report a male neonate born at 28 weeks of gestation. The infant developed skin scaling in the second week of life, which gradually darkened and peeled, primarily over the forehead and upper limbs. Supportive care with emollients and moisturisers was initiated. Genetic testing confirmed STS deletion consistent with XLI. The baby was discharged on day 46 of life and remains under follow-up for monitoring associated issues. Management of XLI is mainly symptomatic, with emphasis on skin hydration, gentle exfoliation, and avoidance of irritants, along with genetic counselling. Emerging therapies such as enzyme replacement and gene therapy are under investigation. Early recognition and confirmation allow timely care, anticipation of complications, and reassurance for families.
2025-12-22 | Gapmer Antisense Oligonucleotide Targeting E-Cadherin Rescues Abnormal Keratinization in X-Linked Ichthyosis Models.
X-linked ichthyosis (XLI) is an inherited disorder of keratinization resulting from a deficiency of steroid sulfatase (STS), for which no effective therapy is currently available. E-cadherin, a key upstream regulator of keratinocyte differentiation, has been found to be markedly overexpressed in STS-deficient HaCaT cells, suggesting its potential as a therapeutic target in XLI. To investigate the functional role of E-cadherin and explore its therapeutic potential, we introduced mutations into the N-terminal region of E-cadherin and examined the resulting effects on keratinocyte differentiation. In addition, a microRNA (miR-6766) and a rationally designed gapmer antisense oligonucleotide (gASO) targeting the same E-cadherin mRNA sequence were employed to modulate E-cadherin expression in HaCaT cells. Mutations within the N-terminal region of E-cadherin significantly reduced keratin 1 expression, underscoring the critical role of this domain in regulating keratinocyte differentiation. Treatment with miR-6766 led to downregulation of both early and terminal differentiation markers. Building on this, the gASO modified with 2'-O-methoxyethyl and phosphorothioate linkages exhibited enhanced potency and stability, resulting in stronger suppression of E-cadherin and keratin 1 expression compared with miR-6766 (maintained 37.7% greater inhibition of E-cadherin at 96 h and 35.7% greater inhibition of keratin 1 at 96 h). Furthermore, gASO treatment induced a concentration-dependent reduction in early (keratin 1 and keratin 10) and terminal (transglutaminase 1, involucrin, and loricrin) differentiation markers. These findings demonstrate that an E-cadherin-targeting gASO effectively suppresses abnormal keratinocyte differentiation and may serve as a promising therapeutic strategy for X-linked ichthyosis.
2026-02-26 | Steroid Sulfatase Deficiency: Clinical Manifestations and Psychological Aspects in Light of Current Evidence.
Syndromic epidermal differentiation disorder associated with steroid sulfatase deficiency (STS-sEDD) is a hereditary disorder of keratinization caused by mutations or deletions in the STS gene. Although historically classified as a dermatological condition, accumulating evidence indicates that STS-sEDD represents a multisystem disorder with significant neuropsychological, endocrine, and cardiological involvement. Psychosocial consequences substantially increase disease burden, highlighting the need for integrated and multidisciplinary care. The aim of this paper is to summarize current knowledge on the biological, clinical, neuropsychological, and psychosocial aspects of STS-sEDD and to identify gaps and challenges in contemporary clinical practice. A purposive, non-systematic review of Polish- and English-language literature published between 1960 and 2025 was conducted. The analysis included articles retrieved from PubMed, Scopus, and Google Scholar databases, as well as materials produced by patient advocacy organizations. Literature selection was carried out in two stages (abstract and full-text review) by two independent reviewers, using keyword sets related to genetic, clinical, neurodevelopmental, and psychosocial domains. Available data indicate that approximately 85-90% of STS-sEDD cases result from complete deletion of the STS gene. Larger deletions within the Xp22.3 region lead to contiguous gene syndromes and are associated with additional manifestations, including attention-deficit/hyperactivity disorder, autism spectrum disorder, endocrine abnormalities, and cardiac arrhythmias. Clinically, STS-sEDD is characterized by typical cutaneous findings accompanied by subtle cognitive and neurodevelopmental deficits, which may also be observed in female carriers. Beyond its medical features, STS-sEDD is associated with stigmatization, reduced quality of life, and significant emotional distress affecting both patients and their families. Evidence suggests that therapeutic education and structured psychological support improve daily functioning and coping. STS-sEDD should therefore be recognized as a multisystem condition requiring early diagnosis and coordinated, interdisciplinary management. The implementation of comprehensive care models has the potential to substantially improve outcomes and quality of life for affected individuals.
2026-01-15 | Early Neonatal presentation of X-linked Ichthyosis – A case report
X-linked ichthyosis (XLI) is an inherited disorder of keratinisation caused by a deficiency of the enzyme steroid sulfatase (STS), leading to accumulation of cholesterol sulfate in the stratum corneum and resulting in retention hyperkeratosis. Affected males typically present in the neonatal period with dark brown, polygonal scales over the trunk, neck, and extensor surfaces, with relative sparing of flexures, face, palms, and soles. Extracutaneous manifestations such as cryptorchidism or corneal opacities may be seen, and larger STS deletions can be associated with neurodevelopmental features. We report a male neonate born at 28 weeks of gestation. The infant developed skin scaling in the second week of life, which gradually darkened and peeled, primarily over the forehead and upper limbs. Supportive care with emollients and moisturisers was initiated. Genetic testing confirmed STS deletion consistent with XLI. The baby was discharged on day 46 of life and remains under follow-up for monitoring associated issues. Management of XLI is mainly symptomatic, with emphasis on skin hydration, gentle exfoliation, and avoidance of irritants, along with genetic counselling. Emerging therapies such as enzyme replacement and gene therapy are under investigation. Early recognition and confirmation allow timely care, anticipation of complications, and reassurance for families.
2025-12-22 | Gapmer Antisense Oligonucleotide Targeting E-Cadherin Rescues Abnormal Keratinization in X-Linked Ichthyosis Models.
X-linked ichthyosis (XLI) is an inherited disorder of keratinization resulting from a deficiency of steroid sulfatase (STS), for which no effective therapy is currently available. E-cadherin, a key upstream regulator of keratinocyte differentiation, has been found to be markedly overexpressed in STS-deficient HaCaT cells, suggesting its potential as a therapeutic target in XLI. To investigate the functional role of E-cadherin and explore its therapeutic potential, we introduced mutations into the N-terminal region of E-cadherin and examined the resulting effects on keratinocyte differentiation. In addition, a microRNA (miR-6766) and a rationally designed gapmer antisense oligonucleotide (gASO) targeting the same E-cadherin mRNA sequence were employed to modulate E-cadherin expression in HaCaT cells. Mutations within the N-terminal region of E-cadherin significantly reduced keratin 1 expression, underscoring the critical role of this domain in regulating keratinocyte differentiation. Treatment with miR-6766 led to downregulation of both early and terminal differentiation markers. Building on this, the gASO modified with 2'-O-methoxyethyl and phosphorothioate linkages exhibited enhanced potency and stability, resulting in stronger suppression of E-cadherin and keratin 1 expression compared with miR-6766 (maintained 37.7% greater inhibition of E-cadherin at 96 h and 35.7% greater inhibition of keratin 1 at 96 h). Furthermore, gASO treatment induced a concentration-dependent reduction in early (keratin 1 and keratin 10) and terminal (transglutaminase 1, involucrin, and loricrin) differentiation markers. These findings demonstrate that an E-cadherin-targeting gASO effectively suppresses abnormal keratinocyte differentiation and may serve as a promising therapeutic strategy for X-linked ichthyosis.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Recessive X-linked ichthyosis.
2 orphan drug designations for Recessive X-linked ichthyosis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Isotretinoin | small molecules | EMA | 2023-02-15 | — | Granzer Regulatory Consulting & Services GmbH |
Talarozole | small molecules | EMA | 2012-07-04 | — | [INACTIVE] Stiefel Laboratories (Maidenhead) Limited |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.