Ichthyosis bullosa of Siemens: report of a family with evidence of a keratin 2e mutation, and a review of the literature

We report a large family with ichthyosis bullosa of Siemens (IBS) including eight affected members spanning three generations. The classical features of the disease were consistently observed with blistering, superficial peel ing of the skin, and localized lichenified hyperkeratosis mainly confined t o the limbs. Phenotypic variation, however, was also observed with some ind ividuals exhibiting unusual clinical features. Specifically the index patie nt was erythrodermic at birth; she subsequently developed a widespread pust ular eruption, Erythroderma is classically absent in IBS and pustulation is very unusual, She also had hypertrichosis of the limbs, as did an affected female first cousin, This has not previously been reported in IBS. Electro n microscopy showed complex aggregates of keratin in the spinous and granul ar layers associated, in places, with remarkably little cell lysis, Sequenc ing of genomic DNA revealed a mutation (E493K) in keratin 2e. A review of t he literature on IBS indicates that E493K is the most commonly reported mut ation to date and might represent a mutational hotspot for this disease.