The role of epidermal proteolysis in overdesquamation was revealed in Netherton syndrome, a rare ichthyosis due to genetic deficiency of the LEKTI inhibitor of serine proteases.
Netherton syndrome (NS) is a rare but severe type of ichthyosis characterized by atopy, allergies, and potentially lethal skin overdesquamation associated with highly elevated proteolytic activities in LEKTI-deficient epidermis.
The known pathogenic molecules involved in ichthyosis syndromes with prominent hair abnormalities include SPINK5, ERCC2, ERCC3, GTF2H5, MPLKIP, ST14, CLDN1 and MBTPS2.
Newborn spink5(R820X/R820X) mice develop a lethal, severe ichthyosis with a loss of skin barrier function and dehydration, resulting in death within a few hours of birth, similar to that observed in patients with severe Netherton syndrome.
Direct SPINK5 mutation analysis in families at risk for NS represents the first early, rapid and reliable method for prenatal diagnosis of this life threatening form of ichthyosis.