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. 2023 Jul 28:14:1213098.
doi: 10.3389/fendo.2023.1213098. eCollection 2023.

Abnormalities of pubertal development and gonadal function in Noonan syndrome

Giuseppa Patti  1   2 , Marco Scaglione  1   2 , Nadia Gabriella Maiorano  1   2 , Giulia Rosti  3 , Maria Teresa Divizia  3 , Tiziana Camia  1   2 , Elena Lucia De Rose  1   2 , Alice Zucconi  1   2 , Emilio Casalini  1   2 , Flavia Napoli  1 , Natascia Di Iorgi  1   2 , Mohamad Maghnie  1   2
Affiliations

Abnormalities of pubertal development and gonadal function in Noonan syndrome

Giuseppa Patti et al. Front Endocrinol (Lausanne). .

Abstract

Background: Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.

Methods: In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.

Conclusions: According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.

Keywords: Noonan syndrome; familial cases; genetic counselling; gonadal function; puberty; vertical transmission.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Zenker M, Edouard T, Blair JC, Cappa M. Noonan syndrome: improving recognition and diagnosis. Arch Dis Child (2022) 107(12):1073–8. doi: 10.1136/archdischild-2021-322858 - DOI - PMC - PubMed
    1. Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet (2013) 381(9863):333–42. doi: 10.1016/S0140-6736(12)61023-X - DOI - PMC - PubMed
    1. Noonan JA. Noonan syndrome and related disorders: alterations in growth and puberty. Rev Endocr Metab Disord (2006) 7(4):251–5. doi: 10.1007/s11154-006-9021-1 - DOI - PMC - PubMed
    1. Tartaglia M, Aoki Y, Gelb BD. The molecular genetics of RASopathies: An update on novel disease genes and new disorders. Am J Med Genet C Semin Med Genet (2022) 190(4):425–39. doi: 10.1002/ajmg.c.32012 - DOI - PMC - PubMed
    1. van der Burgt I. Noonan syndrome. Orphanet J Rare Dis (2007) 2:4. doi: 10.1186/1750-1172-2-4 - DOI - PMC - PubMed

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