CPC14 Winning streak: a case of congenital ichthyosiform erythroderma

Abstract A first-born female infant was delivered at term with widespread redness and scale. There was no family history of genodermatoses or inflammatory dermatoses. There was no parental consanguinity and no history of miscarriages. On examination there was erythroderma, generalized thick adherent scale in a feathery pattern following lines of Blaschko, and shiny red whorls on the dorsolateral feet. There was no skin peeling or skin fragility. Several fingernails were hypoplastic. The nasal bridge was flat and the neck was short. Red reflex was present bilaterally but both eyes were noted to be small. The head and trunk were large relative to the limbs and the proximal limb segments were proportionately short. Given the constellation of signs, a specific syndromic ichthyosis was suspected. Skin biopsies from linear scaly streaks showed orthohyperkeratosis and numerous dilated follicular ostia with keratin plugs. Foci of calcification were seen in the corneocytes of the stratum corneum and hair follicles, highlighted with a von Kossa stain. Skeletal survey showed symmetric punctate calcification and stippling of the proximal femoral epiphysis and ankle bilaterally, and of the right humeral epiphysis and right carpus. These findings were in keeping with chondrodysplasia punctata, although no gross rhizomelia was appreciated radiologically. Ophthalmology review did not identify congenital cataracts. Bloods tests showed normal haematological, renal and bone parameters, and a hyperbilirubinaemia meeting the phototherapy threshold. The erythema was noted to improve markedly following 12 h of phototherapy. Urea 10% cream was helpful in reducing the ichthyosis. Genetic testing revealed a pathogenic variant in the ­emopamil-binding protein (EBP) gene (c.184C>T; p.Arg62Trp), confirming the diagnosis of Conradi–Hünermann–Happle syndrome. Conradi–Hünermann–Happle syndrome is a rare type of chondrodysplasia punctata associated with X-linked dominant mutations in the EBP gene, which impair cholesterol biosynthesis. Affected unborn males are not expected to survive to birth. Conradi–Hünermann–Happle syndrome is characterized by the triad of congenital ichthyosiform erythroderma, skeletal dysplasia and congenital cataracts. The cutaneous phenotype is variable, due to the effects of X-inactivation in female infants. Dystrophic calcifications within keratotic infundibular follicular plugs, especially in the stratum corneum, are a unique but under-recognized histopathological feature of newborns with Conradi–Hünermann–Happle syndrome. It is important to perform the skin biopsy early, as the dystrophic calcifications typically resolve spontaneously after the first few weeks of life. This case highlights a typical dramatic presentation of Conradi–Hünermann–Happle syndrome, and emphasizes the importance of early skin biopsy for diagnostic clues.