Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype

Am J Med Genet. 2001 Sep 15;103(1):75-80. doi: 10.1002/1096-8628(20010915)103:1<75::aid-ajmg1502>;2-r.


Smith-Lemli-Opitz syndrome (RHS) (SLOS, OMIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations of the 3beta-hydroxysterol Delta(7)-Delta(8)-reductase gene, DHCR7. We report a fetus with holoprosencephaly and multiple congenital anomalies who was homozygous for the IVS8-1G-->C mutation. Following termination of pregnancy, both the elevated amniotic fluid 7-dehydrocholesterol level and the DHCR7 mutations were demonstrated. Two other newborn infants with IVS8-1G-->C/IVS8-1G-->C genotype are described. This report illustrates a severe phenotypic extreme of SLOS associated with a null genotype, underscores the complex relationship between SLOS and holoprosencephaly, and discusses the possible pathogenetic mechanisms of the development of holoprosencephaly in SLOS.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • Fatal Outcome
  • Fetal Death
  • Fetus
  • Genotype
  • Holoprosencephaly / pathology
  • Homozygote
  • Humans
  • Infant, Newborn
  • Male
  • Oxidoreductases / genetics
  • Oxidoreductases Acting on CH-CH Group Donors*
  • Point Mutation
  • Smith-Lemli-Opitz Syndrome / genetics*
  • Smith-Lemli-Opitz Syndrome / pathology


  • Oxidoreductases
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase

Associated data

  • OMIM/270400