Ej. Michael et al., Epidermolytic hyperkeratosis with polycyclic psoriasiform plaques resulting from a mutation in the keratin 1 gene, EXP DERMATO, 8(6), 1999, pp. 501-503
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).