Fetal demise with Smith-Lemli-Opitz syndrome confirmed by tissue sterol analysis and the absence of measurable 7-dehydrocholesterol Δ7-reductase activity in chorionic villi

L. M. Linck, S. J. Hayflick, D. S. Lin, K. P. Battaile, S. Ginat, T. Burlingame, K. M. Gibson, M. Honda, A. Honda, G. Salen, G. S. Tint, W. E. Connor, R. D. Steiner

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Smith-Lemli Opitz syndrome (SLOS), an autosomal recessive condition with multiple malformations, mental retardation, and growth failure, results from markedly reduced activity of the final enzyme in the cholesterol biosynthetic pathway, 7-dehydrocholesterol Δ7-reductase (DHCR7). We diagnosed SLOS in a fetus following intrauterine demise at 32 weeks' gestation. Chorionic villus (CV) sampling had been performed at 30 weeks because oligohydramnios and atrioventricular septal defect were noted on fetal ultrasound. On fetal post-mortem examination, a midline U-shaped soft palate cleft, micrognathia, postaxial polydactyly of the fingers with single transverse palmar creases bilaterally, and cutaneous syndactyly of toes two-three bilaterally suggested SLOS. We hypothesized that SLOS could be confirmed by analysis of tissue sterols despite extensive autolysis, and by measurement of enzyme activity in CV cells. Measurement of DHCR7 activity in CV cells was undertaken using ergosterol as a substrate. CV cells were unable to convert any ergosterol to brassicasterol after a 72 h incubation period while control CV cells reduced 12.6-71.8% of ergosterol to brassciasterol in a 72 h period. SLOS was confirmed by measurement of elevated 7-dehydrocholesterol (7-DHC) in the CV cells. Measurements of sterols were made in multiple fetal tissues. All tissues analysed showed elevated 7-DHC with markedly increased 7-DHC/cholesterol ratios. Copyright (C) 2000 John Wiley and Sons, Ltd.

Original languageEnglish (US)
Pages (from-to)238-240
Number of pages3
JournalPrenatal Diagnosis
Volume20
Issue number3
DOIs
StatePublished - Apr 5 2000

Keywords

  • 7-Dehydrocholesterol reductase
  • Metabolic disorder
  • Smith Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Genetics(clinical)

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    Linck, L. M., Hayflick, S. J., Lin, D. S., Battaile, K. P., Ginat, S., Burlingame, T., Gibson, K. M., Honda, M., Honda, A., Salen, G., Tint, G. S., Connor, W. E., & Steiner, R. D. (2000). Fetal demise with Smith-Lemli-Opitz syndrome confirmed by tissue sterol analysis and the absence of measurable 7-dehydrocholesterol Δ7-reductase activity in chorionic villi. Prenatal Diagnosis, 20(3), 238-240. https://doi.org/10.1002/(SICI)1097-0223(200003)20:3<238::AID-PD792>3.0.CO;2-W