Abnormal sterol metabolism in patients with Conradi-Hunermann-Happle syndrome and sporadic lethal chondrodysplasia punctata

Richard I. Kelley, William G. Wilcox, Moyra Smith, Lisa E. Kratz, Ann Moser, David S. Rimoin

Research output: Contribution to journalArticlepeer-review


The term, 'chondrodysplasia punctata' (CDP) denotes a pattern of abnormal punctate calcification of dystrophic epiphyseal cartilage and certain other cartilaginous structures, such as the larynx. CDP occurs in a variety of genetic disorders associated with skeletal dwarfism and can also be caused by prenatal exposure to warfarin. Although the most studied clinical syndrome with CDP, rhizomelic chondrodysplasia punctata (RCDP), is known to be caused by several different abnormalities of pIasmalogen biosynthesis, there are many other genetic disorders with CDP for which the biochemical cause is unknown. Because patients with Smith-Lemli-Opitz syndrome, a primary disorder of sterol biosynthesis, often have rhizomesomelic limb shortness and, less commonly, CDP, we assessed sterol levels and metabolism in patients with different clinical forms of CDP. By quantitative sterol analysis of a variety of tissues, we identified 5 patients with similar radiological findings and abnormally increased levels of 8-dehydrocholesterol and Cholest-8(9)en-3β-ol, suggesting a deficiency of 3β-hydroxysteroid-Δ87-isomerase, a principal enzyme of cholesterol biosynthesis. Cultured cells available from one patient showed increased levels of the same two sterols, decreased synthesis of cholesterol, and a pattern of inhibition by triparanol and AY9944 consistent with a deficiency of 3β-hydroxysteroid-Δ8, Δ7-isomerase. Clinical diagnoses among the 5 patients included X-linked dominant Conradi-Hunermann-Happle syndrome and nonspecific lethal CDP. We conclude that abnormal cholesterol biosynthesis is a characteristic of some clinical syndromes with rhizomesomelic dwarfing and CDP.

Original languageEnglish (US)
Pages (from-to)213-219
Number of pages7
JournalAmerican journal of medical genetics
Issue number3
StatePublished - Mar 19 1999


  • Cholesterol metabolism
  • Chondrodysplasia punctata
  • Rhizomelic dwarfism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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