Epilepsy in Epidermal Nevus Syndromes: Review

Knowledge in the spectrum of epidermal nevi and epidermal nevus syndrome has been elaborated on and expanded rapidly through the years. In this review, we provide a comprehensive overview of the neurologic manifestations of epidermal nevus syndromes (ENS), with a particular focus on epilepsy, which represents one of the most disabling and frequent systemic complications. Although ENS comprises a heterogeneous group of neurocutaneous syndromes unified by the presence of epidermal hamartomas and extracutaneous involvement, the relationship between genotype, cutaneous phenotype, and seizure phenotype remains incompletely understood. We systematically outline the epileptogenic potential of the 10 well-characterized ENS subtypes, highlighting the distinct seizure types, electroencephalographic findings, and associated structural brain anomalies such as hemimegalencephaly, cortical dysplasia, and neuronal heterotopias. Particular emphasis is placed on subtypes with a high seizure burden, including keratinocytic epidermal nevus syndrome, nevus sebaceus syndrome, phakomatosis pigmentokeratotica, nevus comedonicus syndrome, and angora hair nevus syndrome. For each, we examine the available evidence on seizure semiology, electroencephalographic correlates, radiologic features, and outcomes. Additionally, we review current management strategies, including both medical and surgical approaches to epilepsy in ENS, and discuss the emerging role of molecular targeted therapies. Through this review, we aim to underscore the importance of early diagnostic evaluation in patients presenting with epidermal nevi and to support multidisciplinary approaches for seizure control and long-term neurologic outcomes.