About Netherton Syndrome

About Netherton Syndrome

Netherton Syndrome (NS), also referred to as Comèl-Netherton Syndrome, is a debilitating autosomal recessive skin disorder that causes defective keratinization, severe skin barrier defects, and recurrent infections. Patients present shortly after birth with generalized rashes that develop into severe ichthyosis. Infants with more severe NS symptoms are associated with failure to thrive, hypernatremic dehydration secondary to excess fluid loss, delayed growth, short stature, and recurrent infections. Clinically, Netherton Syndrome is characterized by congenital ichthyosiform erythroderma, hair shaft defects, recurrent infections, and a defective skin barrier. Hair shafts are fragile and break easily due to trichorrhexis invaginate, or “bamboo hair”, resulting in short sparse hair. A predisposition to allergies, asthma, and eczema is also characteristic of NS. Ultimately, those afflicted by Netherton Syndrome often experience chronic skin inflammation, severe dehydration, and stunted growth.

The disease arises due to mutations in the Serine Protease Inhibitor Kazal-type 5 (SPINK5) gene, resulting in loss of activity of its encoded serine protease inhibitor protein SPINK5 (also known as Lympho-Epithelial Kazal type-related inhibitor (LEKTI)). In healthy individuals, SPINK5 is one of the serine protease inhibitors expressed in the outermost layers of the skin, and it plays a critical role in the regulation of serine proteases which hydrolyze extracellular proteins that hold corneocytes together. In patients suffering from Netherton Syndrome, the suppressive effects of SPINK5 on these serine proteases is abolished due to underlying genetic mutations in the SPINK5 gene. Consequently, hyperactivated serine proteases in the skin cause uncontrolled desquamation, leading to a defective skin barrier. Unfortunately, there are no currently approved therapies for this disease. Krystal is currently developing KB104 for the treatment of Netherton Syndrome.

For more information on Netherton Syndrome, visit:

Foundation for Ichthyosis & Related Skin Types: http://www.firstskinfoundation.org/types-of-ichthyosis/netherton-syndrome