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Special Feature
Aug 2011

Picture of the Month—Diagnosis

Arch Pediatr Adolesc Med. 2011;165(8):764. doi:10.1001/archpediatrics.2011.120-b

Direct testing by polymerase chain reaction revealed 2 compound heterozygous mutations of the serine protease inhibitor Kazal-type 5 gene (SPINK5) in the proband, one present in his mother and the other in his father. A diagnosis of Comèl-Netherton syndrome was made.

Comèl-Netherton syndrome (OMIM #256500) is an autosomal recessive disease caused by mutations of the SPINK5 gene1 and characterized by the triad of ichthyosis linearis circumflexa, trichorrhexis invaginata, and atopic diathesis. The incidence of Comèl-Netherton syndrome is approximately 1 in 200 000 persons per year. Comèl-Netherton syndrome is also thought to be the cause of up to 18% of congenital erythrodermas2; mortality, mostly due to infections or electrolyte imbalance, is highest during the first year of life. Most patients have mutations in the SPINK5 gene, located on chromosome 5q32, resulting in a loss or reduced expression of the multidomain serine protease inhibitor lymphoepithelial Kazal-type 5 related inhibitor (LEKTI). LEKTI has been proposed to downregulate desquamation and matrix maturation. LEKTI is expressed by epithelial cells of skin, mucosa, and Hassall corpuscles, raising the possibility that LEKTI affects T-cell maturation.3 Although generally not listed among primary immunodeficiencies, a recent study strongly suggests that Comèl-Netherton syndrome is a multisystem disorder associated with dysfunctional innate and cognate immunity.3

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