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BRIEF RESEARCH REPORT article

Front. Endocrinol.

Sec. Neuroendocrine Science

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1527140

This article is part of the Research Topic The Interplay among Brain-Derived Neurotrophic Factor, Sex Hormones, and Brain Function View all 5 articles

Variant pubertal development in Prader-Willi syndrome: Early and slow progression of pubarche with normal age at gonadarche

Provisionally accepted
Aneta Kodytkova Aneta Kodytkova 1*Petra Dusatkova Petra Dusatkova 1Shenali Anne Amaratunga Shenali Anne Amaratunga 1Stanislava Koloušková Stanislava Koloušková 1Barbora Obermannová Barbora Obermannová 1Renata Pomahačová Renata Pomahačová 2Štěpánka Průhová Štěpánka Průhová 1Marta Šnajderová Marta Šnajderová 1Zdenek Sumnik Zdenek Sumnik 1Jiřina Zapletalová Jiřina Zapletalová 3Valerij Semjonov Valerij Semjonov 4Jan Lebl Jan Lebl 1
  • 1 Department of Pediatrics, Second Faculty of Medicine, Charles University, Prague, Czechia
  • 2 Department of Pediatrics, Faculty of Medicine, Charles University and University Hospital Pilsen, Pilsen, Czechia
  • 3 Department of Pediatrics, Faculty of Medicine, Palacky University and Olomouc University Hospital, Olomouc, Czechia
  • 4 Department of statistics, Motol University Hospital, Prague, Czechia

The final, formatted version of the article will be published soon.

    Introduction:Prader-Willi syndrome (PWS) is primarily caused by a paternal microdeletion of the 15q11-q13 region, maternal uniparental disomy (mUPD) or unbalanced translocations.The MKRN3 gene, located within 15q11-q13, is a master regulator of pubertal initiation.We aimed to compare variant pubertal onset and progression with recent normative data and to correlate it with abnormal MKRN3 gene status.Methods:Age at pubarche, gonadarche, subsequent pubertal progression and bone age (BA) at gonadarche were investigated in 37 PWS patients (18 females) who already entered pubarche and/or gonadarche with median age 11.1 (95% CI: 6.4 – 18.8) years.All patients were re-tested to confirm genetic subtypes of PWS.The MKRN3 gene was analyzed using single gene sequencing.Results:Out of 37 subjects, 22 had microdeletion and 15 mUPD.Regardless of genetic subtypes and MKRN3 gene status, no correlation between genotypes and the pubertal pattern was found.They initiated pubarche early – girls at 7.4 (95%CI:6.4–8.4), and boys at 9.2 (8.2–10.2) years.The subsequent progression from PH2 to PH4 (pubic hair development) was prolonged to 3.7 years in girls (1.5–5.9;p<0.05), and 2.9 in boys (2.2–3.6;p<0.001).The age at gonadarche was adequate – 10.0 years in girls (8.8–11.2), and 11.0 in boys (9.8–12.1).Progression rate of breast development from B2 to B4 was 3.9 (0.2–7.5) years in girls and of testicular volume from 4ml to 15ml was 3.8 (0.0–8.1) years in boys.The BA at gonadarche is advanced by 0.6±1.1 years (p<0.001).Conclusions:Children with PWS, regardless of the genetic subtype and/or MKRN3 status, had an early pubarche and normally timed gonadarche.Pubarche progression was slower.Advanced BA was significantly correlated with gonadarche.

    Keywords: ), Zdeněk Šumník 1 ), Jiřina Zapletalová 3 Prader-Willi syndrome, Puberty, Pubarche, Gonadarche, MKRN3 gene

    Received: 12 Nov 2024; Accepted: 25 Mar 2025.

    Copyright: © 2025 Kodytkova, Dusatkova, Amaratunga, Koloušková, Obermannová, Pomahačová, Průhová, Šnajderová, Sumnik, Zapletalová, Semjonov and Lebl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Aneta Kodytkova, Department of Pediatrics, Second Faculty of Medicine, Charles University, Prague, Czechia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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