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Central precocious puberty in a boy with 22q13 deletion syndrome and NOTCH-1 gene duplication

  • Aris Giannakopoulos EMAIL logo , Helen Fryssira , Maria Tzetis , Athina Xaidara and Christina Kanaka-Gantenbein
Published/Copyright: May 28, 2016

Abstract

The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. Central precocious puberty was treated with gonadotropin-releasing hormone (GnRH) analog. Molecular diagnosis with array-comparative genomic hybridization (CGH) revealed a major deletion of 5.8 Mb at the 22q13 chromosomal region and a 25 kb duplication at the 9q34.3 region that included the NOTCH-1 gene. On the background of 22q13 deletion syndrome and data from animals on the effect of abnormal NOTCH-1 gene expression on kisspeptin neuron formation, we discuss the probable role of Notch signaling in the premature activation of the HPG axis.


Corresponding author: Aris Giannakopoulos, MD, PhD, Consultant in Pediatric Endocrinology-Juvenile Diabetes, Division of Endocrinology, Diabetes and Metabolism, Department of Pediatrics, University of Patras, 26500 Rio Patras, Greece, Phone: +30-2610-603-543

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

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Supplemental Material:

The online version of this article (DOI: 10.1515/jpem-2015-0484) offers supplementary material, available to authorized users.


Received: 2015-12-30
Accepted: 2016-4-19
Published Online: 2016-5-28
Published in Print: 2016-11-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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