A review of: Braverman N, Lin P, Moebius FF, et al. 1999 Mutations in the gene encoding 3B-hydroxysteroid-delta8,delta7-isomerase cause X-linked dominant Conradi-Hunermann syndrome. Nat Genet 22:291–294. Derry JMJ, Gormally E, Means GD, et al. 1999 Mutations in a delta8-delta7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. Nat Genet 22:286–290. Kelley RI, Wilcox WG, Smith M, et al. 1999 Abnormal sterol metabolism in patients with Conradi-Hunermann-Happle syndrome and sporadic lethal chondrodysplasia punctata. Am J Med Genet 83:213–219.

RECENT REPORTS OF an association between defective cholesterol biosynthesis and X-linked dominant chondrodysplasia punctata (CDPX2; Conradi-Hunermann-Happle Syndrome) have provided new insight into the link between cholesterol synthesis and skeletal formation (1–3). In a continued search for inherited defects of cholesterolgenesis, Kelley and coworkers extended earlier metabolite studies in Smith-Lemli-Opitz syndrome (SLO; 7-dehydrocholesterol reductase deficiency) to the analysis of plasma sterols in patients with various forms of chondrodysplasia (CDP). The rationale of these studies was based upon the common occurrence of shortening of the proximal/middle limbs and occasional CDP in SLO patients. Physiologic fluids, tissues and cultured cells from five patients revealed significant increases in 8-dehydrocholesterol and cholest-8(9)-en-3B-ol, which suggested a deficiency of 3B-hydroxysteroid-delta8, delta7-isomerase (Xp11.22–11.23; sterol-delta8-isomerase) in two patients with classical CDPX2 and three other patients with severe skeletal disease and less certain clinical diagnoses. In CDPX2 variable Lyonization of an X-linked gene in affected females (the disorder is presumed lethal in males) has long been proposed to explain the asymmetric skeletal pathology, which is not the case in non X-linked forms of CDP.

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