Undetectable maternal serum uE3 and postnatal abnormal sterol and steroid metabolism in Antley-Bixler syndrome

Deborah L. Cragun, Sharon K. Trumpy, Cedric H.L. Shackleton, Richard I. Kelley, Nancy D. Leslie, Neil P. Mulrooney, Robert J. Hopkin

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Antley-Bixler syndrome (ABS) is a rare condition characterized by radiohumeral synostosis, craniosynostosis, midface hypoplasia, bowing of the femora, multiple joint contractures, and urogenital defects. Several reports have implicated errors of steroid or sterol metabolism in the pathogenesis of ABS. Evidence for this has included association with maternal luteomas, fetal 21-hydroxylase deficiency, early pregnancy exposure to high-dose fluconazole, lanosterol 14-α-demethylase deficiency, and a unique urinary steroid profile consistent with apparent pregnene hydroxylation deficiency (APHD). We report two sibs with classic ABS. During both pregnancies, mid-trimester maternal serum screening demonstrated undetectable levels of uncongugated estriol (uE3). The brother had ambiguous genitalia and increased serum levels of progesterone and 17-α-hydroxyprogesterone. Postnatal tests performed on the sister demonstrated both the unique urinary steroid profile that defines APHD and evidence of impaired lanosterol 14-α-demethylase activity. Our results suggest that in at least some patients with ABS, the skeletal findings and altered steroidogenesis are not associated with genes specific to individual sterol or steroid pathways but rather are related to an element, such as NADPH cytochrome P450 reductase (CPR) or cytochrome b5 (CYb5), that is common to all of these pathways.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalAmerican Journal of Medical Genetics
Volume129 A
Issue number1
StatePublished - Aug 15 2004
Externally publishedYes


  • 14-α-demethylase
  • 17-hydroxylase deficiency
  • 21-hydroxylase deficiency
  • Antley-Bixler syndrome
  • Apparent pregnene hydroxylation deficiency
  • Cholesterol
  • Cytochrome p450 reductase
  • Genital ambiguity
  • Low estriol
  • Steroidogenesis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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