X-Linked Dominant Conradi-Hünermann Syndrome: Clinical and Biochemical Phenotype in Affected Males

Principal Investigator: Lisa Kratz

X-Linked Dominant Conradi-Hünermann Syndrome (CPDX2) is a rare disorder of cholesterol biosynthesis caused by a deficiency of 3beta-hydroxysteroid-8, 7-isomerase (sterol isomerase), an enzyme encoded by EBP (emopamil binding protein). Affected heterozygous females present with asymmetric limb shortening, chondrodysplasia punctata, ichthyotic skin changes, and cataracts. Biochemically, a deficiency of sterol isomerase causes increased levels of 8(9)-cholestenol and 8-dehydrocholesterol in plasma and tissues. Prior to the identification of the enzymatic defect, CDPX2 was thought to be lethal in males.

However, through biochemical testing, we have identified 10 males with a sterol profile consistent with a diagnosis of CDPX2. In five of these males, the diagnosis was confirmed by molecular analysis of EBP. While these hemizygous males share some clinical features with affected heterozygous females, the overall clinical phenotype is quite distinct. Common findings in male CDPX2 patients not seen in females include dysmorphic facies, high arched palate, moderate to profound developmental delay, hypotonia, Dandy-Walker variant, and agenesis of the corpus callosum, The purpose of this project is to review and summarize for publication the clinical and biochemical data previously collected for these patients as part of their initial diagnostic evaluation. Data will be collected by the PI and study team member by reviewing the Biochemical Genetics Laboratory diagnostic databases. Available clinical, biochemical, and molecular data will be de-identified and entered into a research database for review. No patient identifiers that would link these data back to the clinical databases will be retained in the research database.