Harlequin ichthyosis: challenges in antenatal diagnosis, neonatal management and outcomes: a case-illustrated systematic review

Abstract

Harlequin ichthyosis is a rare and devastating autosomal recessive congenital disorder characterized by severe hyperkeratosis, profound disruption of the skin barrier and very high neonatal mortality. We performed a systematic review of the literature to synthesize current evidence regarding its genetic basis, antenatal diagnosis, neonatal management and clinical outcomes, and to contextualize these findings using an illustrative case from our institution. A structured search of PubMed, Scopus and Google Scholar was undertaken and relevant studies were reviewed qualitatively. Harlequin ichthyosis is caused predominantly by biallelic mutations in the ABCA12 gene, leading to defective lipid transport and catastrophic impairment of epidermal barrier function. Antenatal diagnosis remains challenging and is frequently missed on routine ultrasound, particularly in the absence of a previously affected child, though late sonographic signs and molecular testing can permit prenatal detection in selected cases. Advances in neonatal intensive care and early use of systemic retinoids have improved survival in some infants; however, mortality remains substantial, especially in resource-limited settings. Our case highlights the dramatic presentation and rapid clinical deterioration when antenatal diagnosis is missed. Early recognition, delivery in a tertiary care setting, aggressive multidisciplinary neonatal management and appropriate genetic counselling remain central to improving outcomes and guiding family decision-making in this otherwise often fatal condition.