Background: X-linked dominant chondrodysplasia punctata, also known as Conradi-Hünermann-Happle syndrome, is a rare skeletal dysplasia characterized by short stature, craniofacial defects, cataracts, ichthyosis, coarse hair, and alopecia. Conradi-Hünermann-Happle syndrome is caused by mutations in the gene EBP encoding Δ(8)-Δ(7) sterol isomerase emopamil-binding protein. Random X-inactivation could account for the intrafamilial variability of the phenotype of X-linked dominant chondrodysplasia punctata.
Observations: We describe a girl with clinical features of X-linked dominant chondrodysplasia punctata. Biochemical analysis showed an abnormal sterol profile consistent with a defect in Δ(8)-Δ(7) sterol isomerase. Molecular studies confirmed the diagnosis by identifying a novel heterozygous missense EBP mutation (c.199C>T; p.Cys67Arg). The mutation was not detectable on genomic DNA extracted from blood lymphocytes in both parents. The mother presented with an erythematous and ichthyosiform skin lesion. EBP analysis of DNA extracted from a lesional skin biopsy revealed the presence of p.Cys67Arg mutation.
Conclusion: To our knowledge, we report the first molecular confirmation of postzygotic mosaicism on an ichthyosiform skin lesion in the mother of a girl with X-linked dominant chondrodysplasia punctata associated with a novel EBP mutation.