| Netherton syndrome | |
|---|---|
| Classification and external resources | |
| ICD-10 | Q80.8 (ILDS Q80.870) |
| ICD-9 | 757.1 |
| OMIM | 256500 |
| DiseasesDB | 30791 |
| eMedicine | derm/431 |
Netherton syndrome is a severe, autosomal recessive[1] form of ichthyosis associated with mutations in the SPINK5 gene.[2][3] It is named after E.W. Netherton.[4]
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Netherton syndrome is characterised by chronic skin inflammation, universal pruritus (itch), severe dehydration and stunted growth. Patients with this disorder tend to have a hair shaft defect (trichorrhexis invaginata), also known as "bamboo hair". The disrupted skin barrier function in affected individuals also presents a high susceptibility to infection and allergy, leading to the development of scaly, reddish skin similar to atopic dermatitis.[5] In severe cases, these atopic manifestations persist throughout the individual's life, and consequently post-natal mortality rates are high. In less severe cases, this develops into the milder ichthyosis linearis circumflexa.[3]
Allergies to nuts and fish are also common amongst affected people but they are not always present in every case.
Netherton syndrome is an autosomal recessive disorder associated with mutations in the SPINK5 gene, which encodes the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI).[2] These mutations result in a dysfunctional protein that has a reduced capacity to inhibit serine proteases expressed in the skin. Potential endogenous targets of LEKTI include KLK5, KLK7 and KLK14.[6] These enzymes are involved in various aspects of epidermal remodelling, including desquamation, PAR-2 activation and degradation of lipid hydrolases, suggesting a potential mechanism for the development of atopic manifestations characteristic of Netherton syndrome.[7]
Disease severity is determined by the level of LEKTI expression and, consequently, serine protease activity. Complete SPINK5 gene deletions have been linked to severe cases, while mutations which induce alternate splicing or create premature stop codons may lead to varying levels of severity.[7] Furthermore, LEKTI-knockout mice exhibit a phenotype similar to Netherton syndrome in humans.[5]
There is no known cure at the moment but there are several things that can be done to relieve the symptoms. moisturising products are very helpful to minimise the scaling/cracking and anti-infective treatments are useful when appropriate because the skin is very susceptible to infection. Extra protein in the diet during childhood is also beneficial to replace that which is lost through the previously mentioned "leaky" skin.
Steroid and retinoid products have been proven ineffective against Netherton syndrome and may in fact make things worse for the affected individual.