Olmsted syndrome caused by heterozygous missense mutation in TRPV3 gene

Olmsted syndrome (OS) is a rare monogenic skin disease characterized by severe keratoderma on the palms, plantae and around natural ori-fices, alopecia, itching and pain syndrome. Pathogenic mutations of the transient receptor potential vanilloid 3 (TRPV3) gene, which encodes the cation-selective ion channel involved in differentiation and proliferation of keratinocytes, processes of hair growth, inflammation, in the per-ception of pain and itching, play the role in the pathogenesis of the disease. Diagnosis of the syndrome can be difficult due to the presence of similar clinical manifestations in other palmoplantar keratodermas, therefore, genetic research is an important part in the approach to managing these complex patients. A case of OS in a 14-year-old girl and experience of therapy with low-dose systemic retinoids are presented. The clinical picture in the patient is represented by a disabling bilateral palmoplantar keratoderma, retarded physical development, osteopo-rosis. In addition, a tendency to the formation of rhagades, cracks in the postauricular folds, anogenital area, fragility and loss of hair, anaemia have been observed. Genetic research has revealed missense mutation in exon 13 of the TRPV3 gene, c.1717GA nucleotide variant in the het-erozygous state leading to p.G573S amino acid variant, described in patients with Olmsted syndrome-1 (OMIM 614594), as well as with the focal non-epidermolytic palmoplantar keratoderma-2 (OMIM 616400), inherited predominantly by autosomal dominant type. Therapy with acitretin was administered for 1 month without effect. Crossover to treatment with systemic isotretinoin at a dose of 20 mg/day in combination with topical keratolytics for 1.5 months led to a reduction in the hyperkeratosis severity in the area of the palms and plantae, regression of cracks in the fold zones. The patient underwent correction of protein-energy malnutrition. As with all serious genetic diseases, families need genetic counseling to discuss the risk of mutations in planning of future pregnancies and possibilities of early prenatal diagnosis. Psychological support and interdisciplinary management of patients with individual approach to the application of available treatment methods are relevant. © 2025 Elsevier B.V., All rights reserved.