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Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?
  1. William Reardona,
  2. Anne Smithb,
  3. John W Honourc,
  4. Peter Hindmarshd,
  5. Debipriya Dasc,
  6. Gill Rumsbyc,
  7. Isabelle Nelsonb,
  8. Sue Malcolmb,
  9. Lesley Adèse,
  10. David Sillencee,
  11. Dhavendra Kumarf,
  12. Celia DeLozier-Blanchetg,
  13. Shane McKeeh,
  14. Thaddeus Kellyi,
  15. Wallace L McKeehanj,
  16. Michael Baraitsera,
  17. Robin M Wintera
  1. aDepartment of Clinical Genetics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK, bMolecular Genetics Unit, Institute of Child Health, London, UK, cDepartment of Chemical Pathology, University College London Hospitals, London, UK, dLondon Centre for Paediatric Endocrinology, University College Hospital, London, UK, eDepartments of Clinical Genetics and Paediatrics and Child Health, New Children's Hospital, Parramatta, NSW 2124, Australia, fCentre for Human Genetics, Sheffield Children's Hospital, 117 Manchester Road, Sheffield S10 5DN, UK, gDivision of Medical Genetics, University of Geneva CMU, 1 rue Michel-Servet CH-1211, Geneva 4, Switzerland, hClinical Genetics Unit, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG UK, iDivision of Medical Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA, jCenter for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A&M University, System Health Science Center, 2121 Holcombe Blvd, Houston, TX 77030, USA
  1. Dr Reardon

Abstract

The Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at theFGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify FGFR2 mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised.

  • Antley-Bixler syndrome
  • FGFR
  • congenital adrenal hyperplasia
  • CYP21 deficiency

https://doi.org/10.1136/jmg.37.1.26

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