Netherton Syndrome

Netherton syndrome is a severe syndromic ichthyosis characterized by congenital erythroderma or ichthyosis linearis circumflexa, the hair-shaft defect trichorrhexis invaginata, failure to thrive, recurrent infection and a marked atopic diathesis with high IgE and food allergy. More info

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Genetics

Autosomal recessive disease caused by biallelic loss-of-function variants in SPINK5, encoding the serine-protease inhibitor LEKTI.

Molecular Mechanism

LEKTI deficiency releases epidermal kallikreins, especially KLK5, KLK7 and KLK14, from normal control. Excess proteolysis accelerates corneodesmosome degradation, activates inflammatory signaling and produces a leaky, highly inflamed epidermal barrier.

Therapy

Care combines emollients, cautious topical anti-inflammatory treatment, infection control, nutritional and allergy management. Intravenous immunoglobulin and targeted biologics can help selected patients, but evidence is limited. Protein, cell and gene-replacement approaches remain investigational.

CCP Activity

CCP develops and phenotypes SPINK5-deficient models and evaluates precise gene-delivery strategies in keratinocyte systems and in vivo. Trans-epidermal water loss, epidermal structure, inflammatory status and restoration of barrier function are used as efficacy endpoints.