Inflammatory linear verrucous epidermal nevus (ILVEN) encompasses a spectrum of inflammatory mosaic disorders.

Background: Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of Blaschko. Two cases of ILVEN with CARD14 mutations and one case with a GJA1 mutation have been previously reported.

Objective: To elucidate the genetic cause of a cohort of patients diagnosed based on clinical and histopathological evaluation with ILVEN.

Methods: We recruited patients diagnosed with ILVEN based on clinical and histopathological criteria. Exome sequencing of affected skin with or without blood/saliva was performed and germline and somatic pathogenic variants were identified.

Results: Five patients were enrolled. All had skin lesions from birth or early childhood. Two patients developed psoriasis vulgaris after the diagnosis of ILVEN. The first had a germline heterozygous CARD14 mutation and a post-zygotic hotspot mutation in KRT10. The histopathologic evaluation did not show epidermolytic hyperkeratosis. The second had a post-zygotic hotspot mutation in HRAS. Her ILVEN became itchy once psoriasis developed. One patient was re-diagnosed with linear porokeratosis based on a germline mutation in PMVK and a post-zygotic second-hit mutation. Two patients were re-diagnosed with congenital hemidysplasia with ichthyosiform nevus and limb defect nevus based on germline NSDHL mutations.

Conclusion: ILVEN is a clinical descriptor for a heterogenous group of mosaic inflammatory disorders. Genetic analysis has the potential to more precisely categorize ILVEN and permits pathogenesis-directed therapies in some cases.