Genotype-phenotype correlation in lipoid proteinosis: 15 cases from Turkiye

Abstract

Introduction: Lipoid proteinosis (LP), a rare autosomal recessive disorder typified by generalized thickening of the skin, mucosa, and certain viscera, is associated with pathogenic ECM1 variants. Skin lesions like beaded eyelid papules, acneiform scars, wavy, yellow papules and nodules typically appear in early childhood. Some patients may exhibit neurological abnormalities like temporal lobe or hippocampiamygdala complex calcification, epilepsy, and neuropsychiatric abnormalities. Methods:We included 15 individuals with LP from 10 unrelated families. The study includes clinical evaluations of family history, radiological findings, histopathological examination of the skin, and genetic investigations. Results: All affected individuals exhibited skin and mucosal lesions. Among the 15 cases, five (33%) showed neurological symptoms, four (26%) presented neuropsychiatric findings, and three (20%) had diabetes mellitus. We observed characteristic intracranial calcifications in all patients with epileptic seizures. Four out of the five cases with epilepsy and intracranial calcifications also had neuropsychiatric findings. All patients with neurological and neuropsychiatric findings had a frame-shift variant, but the same frame-shift variant was not associated with these findings in other individuals. In our study, no patient with variants other than frame-shift variants exhibited neurological or neuropsychiatric findings. Adrenal calcification, which was observed in 1 patient, was not previously linked to LP. Conclusion: Our study observed diverse variations in LP cases among the Turkish population, with varying clinical presentation even among individuals with identical variations within the same family. In our series, the lack of correlation between genotype and phenotype makes providing specific genetic counseling to families challenging. © 2025 Elsevier B.V., All rights reserved.