The evolving genetic landscape of ILVEN: A comprehensive review

Advances in genomics have redefined inflammatory linear verrucous epidermal naevus (ILVEN) as a mosaic inflammatory disorder with diverse molecular drivers, enabling more precise diagnostic and therapeutic strategies. This review aimed to summarize the published data on genotype-phenotype correlations and associated targeted therapies in ILVEN and ILVEN-like disorders. A structured literature search was conducted using PubMed, Embase and Google Scholar, focusing on peer-reviewed studies describing mutations, pathomechanisms and treatment responses in ILVEN or ILVEN-mimicking dermatoses. Search terms included "ILVEN", "mosaic inflammatory dermatoses", "genetic mutations" and "targeted therapy". Multiple genes have been implicated in ILVEN. Somatic mutations in CARD14 activate NF-κB and IL-12/23/IL-17 signalling pathways and may be responsive to biologics such as secukinumab and ustekinumab. Mutations in NSDHL and PMVK, involved in cholesterol biosynthesis, are associated with ILVEN-like presentations and may respond to topical statin/cholesterol therapy. KRT10 mutations, which affect keratinocyte differentiation, show favourable responses to crisaborole and acitretin. GJA1 mutations disrupt connexin 43 function, resulting in ILVEN-Erythrokeratodermia Variabilis et Progressiva (EKVP) overlap and may respond to retinoids. HRAS mosaicism activates the RAS-MAPK pathway, supporting the theoretical use of MEK inhibitors. Recessive mosaicism in ABCA12 can produce linear, ILVEN-like lesions due to defective lipid barrier formation, with potential responsiveness to lipid-replenishing therapies and IL-17 blockade. The molecular characterization of ILVEN and related disorders supports a shift toward precision dermatology. As accessibility increases, genotype-directed therapy may replace empiric approaches with more targeted, effective and personalized management frameworks.