title: Ichthyosis Linearis Circumflexa as the Only Clinical Manifestation of Netherton Syndrome.
abstract: Ichthyosis linearis circumflexa (ILC) presents as serpiginous and migratory erythematous patches with double-edged scales. ILC is rarely an isolated skin manifestation, but most commonly a part of Netherton syndrome (NS). NS is caused by SPINK5 mutations, which lead to absent or sometimes reduced expression of the serine protease inhibitor LEKTI. NS is characterised by congenital ichthyosiform erytroderma, trichorrhexis invaginata (TI) and atopy. We report 2 children who presented since the first months of life cheek erythema followed by the appearance of sparse ILC lesions on the face, trunk and proximal extremities. Erythroderma at birth, TI and atopy were absent. LEKTI immunoreactivity was reduced in patient epidermis, and serine protease activity was modestly increased, while desmoglein-1 expression remained unaffected. SPINK5 mutation and expression analysis in patient keratinocytes revealed compound heterozygous splicing variants, which allowed residual LEKTI secretion. Our results show that ILC can be the only clinical manifestation of NS.
authors.affiliation: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, 00167 Rome, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Guerra
authors.forename: Paola
authors.initials: P
authors.lastname: Fortugno
authors.forename: Cristina
authors.initials: C
authors.lastname: Pedicelli
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mazzanti
authors.forename: Vittoria
authors.initials: V
authors.lastname: Proto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
mesh_terms: D002675:Child, Preschool; D051183:Desmoglein 1 / Q000032:analysis; D004817:Epidermis / Q000737:chemistry* / Q000201:enzymology; D005260:Female; D006801:Humans; D007057:Ichthyosis / Q000209:etiology*; D007223:Infant; D008297:Male; D009154:Mutation; D056770:Netherton Syndrome / Q000150:complications* / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000032:analysis* / Q000235:genetics*; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D057057:Serine Proteases / Q000378:metabolism
chemical_list: D051183:Desmoglein 1; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D057057:Serine Proteases