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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma


IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

SCImago Journal Rank (SJR) 2018: 0.507
Source Normalized Impact per Paper (SNIP) 2018: 0.562

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2191-0251
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Volume 29, Issue 7

Issues

Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene

Manish Raisingani
  • Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA
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/ Maria F. Contreras
  • Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA
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/ Kris Prasad
  • Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA
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/ John G. Pappas
  • Department of Pediatrics, Clinical Genetic Services, New York University School of Medicine, New York, NY, USA
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/ Michelle L. Kluge / Bina Shah
  • Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA
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/ Raphael David
  • Corresponding author
  • Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA
  • Email
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Published Online: 2016-05-16 | DOI: https://doi.org/10.1515/jpem-2015-0457

Abstract

Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies.

Keywords: congenital adrenal hyperplasia (CAH); novel mutation; precocious puberty

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About the article

Corresponding author: Raphael David, MD, Bellevue Hospital, 462 First Avenue, 8th Floor, Room 8 West 52, New York, NY 10016, USA, Phone: 212-263-6462, Fax: 212-562-3273


Received: 2015-11-28

Accepted: 2016-02-22

Published Online: 2016-05-16

Published in Print: 2016-07-01


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 29, Issue 7, Pages 867–871, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2015-0457.

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