Epidermolytic hyperkeratosis with polycyclic psoriasiform plaques resulting from a mutation in the keratin 1 gene

Epidermolytic hyperkeratosis (EHK) is a genodermatosis caused by mutations in either the keratin 1 (K1) or keratin 10 (K10) genes, and characterized b y erythroderma and blistering at birth, with development of a ribbed, ichth yotic hyperkeratosis and palmoplantar keratoderma. A wide variety of mutati ons within the highly conserved helix termination motifs of the central rod domains of the K1 or K10 genes correlate with the highly variable phenotyp ic severity observed in EHK. We report a unique EHK-like phenotype exhibiti ng autosomal dominant inheritance with variable expressivity in four affect ed individuals in a single family. Clinically, affected individuals manifes t transient blistering at birth followed by chronic diffuse palmoplantar ke ratoderma without transgradiens. Intermittent hares of non-migratory polycy lic erythematous psoriasiform plaques which worsen and abate in severity we re present in all affected individuals, but showed immense individual varia tion in both severity and duration, ranging from weeks to months. Histopath ologic examination of the psoriasiform plaques demonstrated the characteris tic features of EHK. Sequencing of the K1 gene in affected family members r evealed a heterozygous A-to-T transversion at nucleotide 1435 within exon 7 , converting isoleucine (ATT) to phenylalanine (TK), (I479F). The mutation resides within the highly conserved helix termination motif of the helix 2B segment of the K1 gene. This unique clinical phenotype and the associated K1 mutation have not been previously described, and it is referred to here as EHK with polycyclic, psoriasiform plaques (EHK/PPP).