Patients with X-linked chondrodysplasia punctata (CDPX2) [OMIM #302960], also known as Happle syndrome or Conradi-Hünermann syndrome, have asymmetric shortening of the limbs, scoliosis, and widespread epiphyseal stippling, usually including the vertebral column and tracheal cartilage. Another classic finding includes various skin abnormalities, like erythema and scaling “oat bran” ichthyosis in the newborn period or atrophoderma and ichthyosis in older children.
Mutations of the EBP [OMIM #300205] gene, or emopamil binding protein, have been identified in patients with CDPX2. Patients with CDPX2 have increased tissue or plasma levels of 8(9)-cholestenol and 8-dehydrocholesterol. Sterol analysis of plasma and scales from skin lesions is currently used for diagnosis and is available at the Clinical Mass Spectrometry Laboratory at Kennedy Krieger Institute. This test may also distinguish CDPX2 from CHILD syndrome, a phenotypically similar condition caused by mutations in the NSDHL (NADH steroid dehydrogenase-like) gene. Unpublished data in Dr. Richard Kelley’s lab shows that approximately 95% of patients with these biochemical findings are found to have a mutation in the EBP gene.
To date no deletions or duplications involving the EBP gene as causative of CDPX2 have been reported.