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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Pediatric Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1531545
This article is part of the Research Topic Endocrine Aspects of Noonan Syndrome and Related Syndromes: Volume II View all 5 articles

Impact of Pubertal Timing on Growth Progression and Final Height in Subjects affected by RASopathies

Provisionally accepted
Federica Tamburrino Federica Tamburrino 1*Laura Mazzanti Laura Mazzanti 2Dino Gibertoni Dino Gibertoni 3Concetta Schiavariello Concetta Schiavariello 1annamaria perri annamaria perri 1eleonora orlandini eleonora orlandini 1Cesare Rossi Cesare Rossi 4Marco Tartaglia Marco Tartaglia 5Marcello Lanari Marcello Lanari 1Emanuela Scarano Emanuela Scarano 1
  • 1 Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  • 2 University of Bologna, Bologna, Emilia-Romagna, Italy
  • 3 Statistics and Epidemiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  • 4 Medical Genetics Unit, IRCSS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Bologna, Emilia-Romagna, Italy
  • 5 Molecular Genetics and Functional Genomics Unit, Bambino Gesù Children's Hospital (IRCCS), Roma, Italy

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

    Background RASopathies, including Noonan syndrome and related disorders, are multisystem conditions caused by mutations in various genes encoding proteins involved in the RAS/MAPK signaling pathway resulting in increased signal flow. They are clinically characterized by failure to thrive, facial dysmorphisms, congenital heart defects, lymphatic malformations, skeletal anomalies, and variable cognitive impairment, with variable prevalence in the different conditions and subtypes. Pubertal development, which affects growth and final height, is often delayed in Noonan syndrome patients, though not universally. This study aimed to evaluate the timing and progression of puberty and its impact on growth and final height in patients with RASopathies. Subjects and Methods A retrospective longitudinal study was conducted involving 103 patients with molecularly confirmed RASopathies. A subgroup of 40 patients who had completed pubertal development was analyzed. Anthropometric, hormonal (FSH, LH, estradiol/testosterone), and radiological data were collected. Results Among the 40 patients who had completed puberty, 75% had a diagnosis of Noonan syndrome. The median age at pubertal onset was 11.8 years in males and 13.2 years in females. Delayed puberty was observed in 27.8% of patients, with a higher incidence in females. Median final height was significantly lower in those with delayed pubertal onset compared to those with normal development (p < 0.01). No significant differences in final height were observed between patients with growth hormone deficiency treated with growth hormone and those who were untreated. Conclusions Delayed pubertal onset negatively impacts final height in patients with RASopathies, with inadequate pubertal catch-up growth being a common outcome. While most patients initiate puberty spontaneously, careful monitoring of growth and pubertal progression is crucial to optimize therapeutic interventions and improve final height outcomes.

    Keywords: Noonan Syndrome, mazzanti syndrome, RASopathies, Puberty, Growth Hormone

    Received: 20 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Tamburrino, Mazzanti, Gibertoni, Schiavariello, perri, orlandini, Rossi, Tartaglia, Lanari and Scarano. 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: Federica Tamburrino, Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

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