Clinical Report

Boy with pseudohypoparathyroidism type 1a caused by GNAS gene mutation (deltaN377), Crouzon-like craniosynostosis, and severe trauma-induced bleeding†‡

  1. Luitgard M. Graul-Neumann1,2,*,
  2. Alexia Bach3,
  3. Michael Albani3,
  4. Hannelore Ringe4,
  5. Andreas Weimann5,
  6. Wolfram Kress6,
  7. Olaf Hiort7,
  8. Oliver Bartsch8

Article first published online: 15 JUN 2009

DOI: 10.1002/ajmg.a.32889

Issue

American Journal of Medical Genetics Part A

American Journal of Medical Genetics Part A

Volume 149A, Issue 7, pages 1487–1493, July 2009

Additional Information

How to Cite

Graul-Neumann, L. M., Bach, A., Albani, M., Ringe, H., Weimann, A., Kress, W., Hiort, O. and Bartsch, O. (2009), Boy with pseudohypoparathyroidism type 1a caused by GNAS gene mutation (deltaN377), Crouzon-like craniosynostosis, and severe trauma-induced bleeding. American Journal of Medical Genetics Part A, 149A: 1487–1493. doi: 10.1002/ajmg.a.32889

Author Information

  1. 1

    Institute of Medical Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany

  2. 2

    Institute of Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany

  3. 3

    Department of Pediatrics, Dr. Horst Schmidt-Kliniken, Wiesbaden, Germany

  4. 4

    Department of Pediatrics, Charité Universitätsmedizin Berlin, Berlin, Germany

  5. 5

    Central Institute of Laboratory Medicine and Pathobiochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany

  6. 6

    Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany

  7. 7

    Department of Pediatrics, University of Lübeck, Lübeck, Germany

  8. 8

    Institute of Human Genetics, Johannes Gutenberg-Universität Mainz, Mainz, Germany

*Institute of Medical Genetics, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.

  1. †

    Luitgard M. Graul-Neumann and Alexia Bach contributed equally to this article.

  2. ‡

    How to cite this article: Graul-Neumann LM, Bach A, Albani M, Ringe H, Weimann A, Kress W, Hiort O, Bartsch O. 2009. Boy with pseudohypoparathyroidism type 1a caused by GNAS gene mutation (deltaN377), Crouzon-like craniosynostosis, and severe trauma-induced bleeding. Am J Med Genet Part A 149A:1487–1493.

Publication History

  1. Issue published online: 18 JUN 2009
  2. Article first published online: 15 JUN 2009
  3. Manuscript Accepted: 23 MAR 2009
  4. Manuscript Received: 25 SEP 2008

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Keywords:

  • GNAS complex;
  • pseudohypoparathyroidism;
  • craniosynostosis

Abstract

We report on a 6-month-old boy with craniosynostosis, pseudohypoparathyroidism type 1a (PHP1A), and a GNAS gene mutation. He had synostoses of the coronal, frontal, and sagittal sutures, brachyturricephaly, and hydrocephaly. He also had congenital hypothyroidism, round face, full cheeks, shortness of limbs, mild developmental delay, and muscular hypotonia. Because of progressive hydrocephaly, the synostosis was corrected surgically but circulatory decompensation led to disseminated intravascular coagulation and cerebral infarctions. Our patient died 8 days later. Postmortem molecular studies of GNAS, the gene for guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (gene for PHP1A), identified a de novo heterozygous 3 bp in frame deletion predicting a deletion of the asparagine residue at position 377 (deltaN377). This is the second report of this mutation. Results of molecular studies of craniosynostosis genes (FGFR2, FGFR3) and of numerous genetic variants predisposing to bleeding disorders were normal. We question whether craniosynostosis and trauma-induced bleeding disorder may be manifestations of PHP1A, or if our patient had two or three different congenital disorders. © 2009 Wiley-Liss, Inc.

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