Familial Darier Disease Across 3 Generations: Highlighting the Spectrum of Neuropsychiatric Comorbidities.

Abstract

Abstract: Darier disease (DD) is a rare genodermatosis caused by mutations in the ATP2A2 gene, leading to impaired intracellular calcium signaling, acantholysis, and dyskeratosis. Although traditionally viewed primarily as a cutaneous disorder, DD shows significant intragenerational and intergenerational phenotypic variability and systemic associations. We present an extraordinary case series of 3 patients from a single Turkish family representing 3 successive generations of DD, each demonstrating distinct clinical manifestations alongside varying neuropsychiatric comorbidities. Specifically, the first-generation patient presented with Alzheimer disease, the second with obsessive-compulsive disorder, and the third with cognitive impairment. The diagnosis was supported by classical clinical and histopathological findings. To our knowledge, this is the first report specifically characterizing the spectrum of neuropsychiatric manifestations across 3 consecutive generations within a single family affected by DD. This familial presentation highlights the disease's complex pleiotropic effects and underscores the need for a multidisciplinary approach to evaluating these patients.