Steroid Sulfatase Deficiency: Clinical Manifestations and Psychological Aspects in Light of Current Evidence

Abstract: 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. Keywords: X-linked ichthyosis, STS gene, contiguous gene syndrome