✍ Scribed by Kelley, Richard I.; Wilcox, William G.; Smith, Moyra; Kratz, Lisa E.; Moser, Ann; Rimoin, David S.
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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 plasmalogen 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-3-ol, suggesting a deficiency of 3hydroxysteroid-⌬ 8 ,⌬ 7 -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 AY-9944 consistent with a deficiency of 3-hydroxysteroid-⌬ 8 ,⌬ 7 -isomerase. Clinical diagnoses among the 5 patients included Xlinked dominant Conradi-Hu ¨nermann-Happle syndrome and nonspecific lethal CDP. We conclude that abnormal cholesterol biosynthesis is a characteristic of some clinical syndromes with rhizomesomelic dwarfing and CDP.
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In the second paragraph of the "Discussion" section, an incorrect chromosome segment is given for the locus of the human sterol-⌬ 8 -isomerase gene. The correct site is 11p11.22-23.
Chondrodysplasia punctata (CDP) is associated with a variety of genetic and nongenetic conditions. We report a girl with CDP, complex congenital cardiac disease, central nervous system (CNS) anomalies, and clinical findings that resemble those of the sibs described by Toriello et al. [
We describe a girl with Niikawa-Kuroki (Kabuki) syndrome (NKS) with conical incisors, hypodontia, hypoplastic nails, and brittle hair. Abnormal teeth are common in NKS and support a hypothesis of autosomal dominant inheritance of the syndrome [Halal et al., 1989; Silengo et al., 1996]. Hair abnormal
We analyzed the total hand length (HL) and length of noncarpal bones (NCL) in 50 Japanese patients with Ullrich-Turner syndrome (UTS) and in 443 other patients with short stature used as controls. In each patient group we calculated relative HL (RHL= HL/ height) and relative NCL (RNCL= NCL/ height).
The finding of stippled epiphyses on a neonatal radiograph generates a wide differential diagnosis, including genetic and teratogenic causes. We report the case of a male infant with stippled epiphyses evident on neonatal radiographs in whom a typical rash of lupus erythematosus developed. The skin
This love story for the ages, set in a reimagined industrial Asia, is a little dark, a bit breathless, and completely compelling. Sixteen-year-old Wen assists her father in his medical clinic, housed in a slaughterhouse staffed by the Noor, men hired as cheap factory labor. Wen often hears the