Ichthyosis: Inherited Disorders of Keratinization

Overview / Definition Ichthyosis is a term used to describe a heterogeneous group of inherited disorders of keratinization. It is characterized by dry, thickened, and scaly skin resulting from abnormal keratinocyte function. The various forms of ichthyosis can range from mild to severe, with some subtypes associated with systemic involvement. Epidemiology Ichthyosis affects approximately 1 in 250 to 1 in 300 births, though the prevalence can vary based on the specific subtype. The most common form, ichthyosis vulgaris, is estimated to affect 1 in 250 individuals. Other forms, such as lamellar ichthyosis and epidermolytic ichthyosis, occur with lower frequency. Pathophysiology / Mechanism The pathophysiology of ichthyosis varies by subtype; however, all forms share a common defect in the process of keratinization. In ichthyosis vulgaris, mutations in the filaggrin gene (FLG) disrupt the formation of the skin barrier, leading to increased transepidermal water loss and abnormal scaling. In lamellar ichthyosis, mutations in the ABCA12 gene result in impaired lipid transport, while epidermolytic ichthyosis is caused by keratin mutations affecting the structural integrity of the epidermis. Clinical Presentation Patients with ichthyosis can present with a variety of symptoms depending on the subtype. Common clinical features include: Dry, scaly skin: Ranging from fine scaling in ichthyosis vulgaris to large, plate-like scales in lamellar ichthyosis. Hyperlinearity: Increased skin markings, especially on palms and soles. Pruritus: Commonly associated with dry skin, particularly in ichthyosis vulgaris. Other systemic manifestations: In some forms, such as X-linked ichthyosis, patients may have associated ocular or systemic issues. Diagnosis / Workup The diagnosis of ichthyosis is primarily clinical, based on the characteristic appearance of the skin. However, genetic testing can confirm specific subtypes and mutations. Key steps in the workup include: Clinical examination: A