Netherton syndrome: interdisciplinary approach by dermatologists, immunologists and geneticists

Netherton syndrome (OMIM #256500) is a rare autosomal recessive syndrome, characterized by erythroderma, parakeratosis, trichorrhexis invaginate, also known like «bamboo hairs», immunodefciciency, atopic manifestations and hypereosinophilia. Correlations between genotype and phenotype have been observed in patients with Netherton syndrome: variants located closer to the 5′-untranslated region of the gene are associated with more severe phenotypes, while variants closer to the 3′-end of the gene are linked to milder phenotype. No patients with biallelic variants in exons 29-33 have been described in the literature, suggesting a possible unknown compensatory mechanism. This study presents a case of a patient with dermatological and immunological manifestations, harboring a previously unreported homozygous variant in exon 23 of the SPINK5 gene, which may be associated with a relatively mild disease. This clinical case underscores the need for a multidisciplinary approach in managing Netherton syndrome patients and the need for further studiesto better understand the pathogenesis of the disease and explore potential therapeutic strategies.

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