Ichthyosis and Keratotic Follicular Plugs Containing Dystrophic Calcification in Newborns: Distinctive Histopathologic Features of X-Linked Dominant Chondrodysplasia Punctata (Conradi-Hünermann-Happle Syndrome)

Prior to the recent characterization of the enzymatic defect and identification of the involved gene, the histopathology of X-linked dominant chondrodysplasia punctata (Conradi-Hünermann-Happle syndrome or CDPX2) has been described under various names including calcinosis universalis, chondrodystrophia calcificans congenita, Conradi disease, and Conradi-Hünermann syndrome. We present two newborns with characteristic ichthyosiform erythrodemia noted at birth. Radiographs demonstrated chondrodysplasia punctata in one patient. Although the x-ray performed at birth was negative in the other patient, sterol analyses of the keratotic scales were diagnostic for CDPX2. Skin biopsies from both patients showed thick laminated orthokeratosis and prominent keratotic follicular plugs containing dystrophic calcification. We also retrospectively examined 20 cases of various types of ichthyosis seen over a 23-year period at our institution. Intracorneal calcium deposition was not seen in any of these cases. As demonstrated by our cases and review of the literature, dystrophic calcification in the keratotic plug is a distinctive histopathologic feature of Conradi-Hünermann-Happle syndrome in newborns and is not seen in other known forms of ichthyoses.