---
title: "Cranial abnormalities in Noonan syndrome: implications for pre–growth hormone cranial MRI"
id: "pubmed-42665698"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42665698"
content_type: "clinical_feed_article"
specialty: "Pediatrics"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42665698/"
doi: "10.1007/s00431-026-07361-z"
published_at: "2026-08-29T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Cranial abnormalities in Noonan syndrome: implications for pre–growth hormone cranial MRI
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42665698
- **Specialty:** [Pediatrics](https://medichelpline.com/clinical-feed/pediatrics.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42665698/)
- **DOI:** [10.1007/s00431-026-07361-z](https://doi.org/10.1007%2Fs00431-026-07361-z)
- **Published At:** 2026-08-29T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Noonan syndrome (NS) is a multisystem disorder caused by mutations in the **RAS–MAPK pathway** and carries an increased risk of proliferative disorders. - This retrospective cross-sectional study reviewed clinical, anthropometric, laboratory, and cranial MRI data from patients with NS followed between January 2000 and January 2025. - Cranial abnormalities were identified in **54.1%** of patients with NS, spanning a spectrum from structural anomalies to clinically significant intracranial tumors. - Some lesions were asymptomatic, indicating that routine clinical assessment alone may miss relevant intracranial pathology. - No newly detected pathologies or malignancies were reported during follow-up in patients receiving recombinant **growth hormone therapy**, supporting its safety in this cohort. - The authors conclude that **cranial MRI at diagnosis** should be considered to enable early identification of clinically relevant intracranial abnormalities, particularly before initiating growth hormone treatment. - Study methods included retrospective review and statistical analysis with SPSS version 29.0; ethical approval was obtained from the Ankara University Human Research Ethics Committee. - The report notes limited prior data on cranial MRI findings in NS, with previous evidence derived mainly from small series; this study adds a larger cross-sectional dataset spanning 25 years. - Keywords emphasized by the authors include **cranial MRI**, central nervous system tumors, cranial abnormalities, growth hormone therapy, Noonan syndrome, and RAS–MAPK pathway.
## Clinical Analysis & Structured Key Points
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Cranial pathologies in Noonan syndrome: clinical implications for pre-growth hormone neuroimaging [Emine Kübra Şen](https://pubmed.ncbi.nlm.nih.gov/?term=%C5%9Een+EK&cauthor_id=42665698)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-1 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey. eksen@ankara.edu.tr."), [Sirmen Kızılcan Çetin](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%87etin+SK&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Seda Kaynak Şahap](https://pubmed.ncbi.nlm.nih.gov/?term=%C5%9Eahap+SK&cauthor_id=42665698)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-3 "Division of Pediatric Radiology, Department of Radiology, Ankara University Faculty of Medicine, Ankara, Turkey."), [Ömer Suat Fitöz](https://pubmed.ncbi.nlm.nih.gov/?term=Fit%C3%B6z+%C3%96S&cauthor_id=42665698)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-3 "Division of Pediatric Radiology, Department of Radiology, Ankara University Faculty of Medicine, Ankara, Turkey."), [İbrahim Dikmen](https://pubmed.ncbi.nlm.nih.gov/?term=Dikmen+%C4%B0&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Eda Didem Kayakıran](https://pubmed.ncbi.nlm.nih.gov/?term=Kayak%C4%B1ran+ED&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Sema Nilay Abseyi](https://pubmed.ncbi.nlm.nih.gov/?term=Abseyi+SN&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Şafak Demirtaş](https://pubmed.ncbi.nlm.nih.gov/?term=Demirta%C5%9F+%C5%9E&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [İlkyaz Türktan](https://pubmed.ncbi.nlm.nih.gov/?term=T%C3%BCrktan+%C4%B0&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Elif Özsu](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%96zsu+E&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Zehra Aycan](https://pubmed.ncbi.nlm.nih.gov/?term=Aycan+Z&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Zeynep Şıklar](https://pubmed.ncbi.nlm.nih.gov/?term=%C5%9E%C4%B1klar+Z&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#full-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey.") Affiliations Expand ### Affiliations * 1 Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey. eksen@ankara.edu.tr. * 2 Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey. * 3 Division of Pediatric Radiology, Department of Radiology, Ankara University Faculty of Medicine, Ankara, Turkey. * PMID: **42665698** * DOI: [ 10.1007/s00431-026-07361-z ](https://doi.org/10.1007/s00431-026-07361-z) Item in Clipboard # Cranial pathologies in Noonan syndrome: clinical implications for pre-growth hormone neuroimaging Emine Kübra Şen et al. Eur J Pediatr. 2026. Show details Display options Display options Format Abstract PubMed PMID Eur J Pediatr Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+J+Pediatr%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+J+Pediatr%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42665698/) . 2026 Aug 29;185(9):700. doi: 10.1007/s00431-026-07361-z. ### Authors [Emine Kübra Şen](https://pubmed.ncbi.nlm.nih.gov/?term=%C5%9Een+EK&cauthor_id=42665698)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-1 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey. eksen@ankara.edu.tr."), [Sirmen Kızılcan Çetin](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%87etin+SK&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Seda Kaynak Şahap](https://pubmed.ncbi.nlm.nih.gov/?term=%C5%9Eahap+SK&cauthor_id=42665698)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-3 "Division of Pediatric Radiology, Department of Radiology, Ankara University Faculty of Medicine, Ankara, Turkey."), [Ömer Suat Fitöz](https://pubmed.ncbi.nlm.nih.gov/?term=Fit%C3%B6z+%C3%96S&cauthor_id=42665698)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-3 "Division of Pediatric Radiology, Department of Radiology, Ankara University Faculty of Medicine, Ankara, Turkey."), [İbrahim Dikmen](https://pubmed.ncbi.nlm.nih.gov/?term=Dikmen+%C4%B0&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Eda Didem Kayakıran](https://pubmed.ncbi.nlm.nih.gov/?term=Kayak%C4%B1ran+ED&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Sema Nilay Abseyi](https://pubmed.ncbi.nlm.nih.gov/?term=Abseyi+SN&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Şafak Demirtaş](https://pubmed.ncbi.nlm.nih.gov/?term=Demirta%C5%9F+%C5%9E&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [İlkyaz Türktan](https://pubmed.ncbi.nlm.nih.gov/?term=T%C3%BCrktan+%C4%B0&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Elif Özsu](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%96zsu+E&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Zehra Aycan](https://pubmed.ncbi.nlm.nih.gov/?term=Aycan+Z&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey."), [Zeynep Şıklar](https://pubmed.ncbi.nlm.nih.gov/?term=%C5%9E%C4%B1klar+Z&cauthor_id=42665698)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665698/#short-view-affiliation-2 "Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey.") ### Affiliations * 1 Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey. eksen@ankara.edu.tr. * 2 Division of Pediatric Endocrinology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey. * 3 Division of Pediatric Radiology, Department of Radiology, Ankara University Faculty of Medicine, Ankara, Turkey. * PMID: **42665698** * DOI: [ 10.1007/s00431-026-07361-z ](https://doi.org/10.1007/s00431-026-07361-z) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Noonan syndrome (NS) is a multisystem disorder caused by mutations affecting the RAS-MAPK signaling pathway and is associated with an increased risk of proliferative disorders. This study aimed to evaluate the frequency and spectrum of cranial pathologies in patients with NS and to assess their clinical significance. This cross-sectional study included patients with NS followed between January 2000 and January 2025. Clinical, anthropometric, laboratory, and cranial MRI data obtained at diagnosis and during follow-up were retrospectively reviewed. Statistical analyses were performed using SPSS version 29.0. Cranial abnormalities were identified in 54.1% of patients with NS. The identified abnormalities ranged from structural anomalies to clinically significant intracranial tumors. The asymptomatic nature of some lesions suggests that clinical evaluation alone may be insufficient. The absence of newly detected pathologies or malignancies during follow-up in patients receiving growth hormone therapy supports its safety. These findings support consideration of cranial MRI at the time of diagnosis in patients with NS. **Conclusion:** Cranial abnormalities are common in patients with NS and encompass a broad spectrum ranging from structural anomalies to clinically significant neoplastic lesions. The presence of asymptomatic lesions suggests that clinical evaluation alone may be insufficient for their detection. Cranial MRI at the time of diagnosis may facilitate the early identification of clinically relevant intracranial abnormalities. The absence of malignancy during follow-up supports the safety of recombinant growth hormone therapy in this population. **What is known:** • Noonan syndrome is associated with abnormalities of the RAS-MAPK signaling pathway and an increased risk of proliferative disorders. • Data regarding cranial MRI findings in patients with Noonan syndrome are limited and mainly derived from small case series. **What is new:** • More than half of the patients with Noonan syndrome had cranial MRI abnormalities, including a broad spectrum of structural lesions and clinically significant intracranial neoplasms. • Clinically significant lesions may remain asymptomatic, supporting consideration of cranial MRI at the time of diagnosis, particularly before initiation of growth hormone therapy. **Keywords:** Central nervous system tumors; Cranial MRI; Cranial abnormalities; Growth hormone therapy; Noonan syndrome; RAS–MAPK pathway. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval for this study was obtained from the Ankara University Faculty of Medicine Human Research Ethics Committee (approval number: İ01-104–70). Consent for publication: The authors affirm that human research participants provided informed consent for publication of the images in Figs. 1, 2, and 3. Competing interests: The authors declare no competing interests. ## Similar articles * [ Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy. ](https://pubmed.ncbi.nlm.nih.gov/26377682/) McWilliams GD, SantaCruz K, Hart B, Clericuzio C.McWilliams GD, et al.Am J Med Genet A. 2016 Jan;170A(1):195-201. doi: 10.1002/ajmg.a.37379. Epub 2015 Sep 17.Am J Med Genet A. 2016.PMID: 26377682Review. * [ Neuroimaging Abnormalities and Genotype-Phenotype Correlations in Noonan Syndrome: A Multicenter Cohort Study. ](https://pubmed.ncbi.nlm.nih.gov/42657773/) Patti G, Maiorano NG, Piccoli F, Zucconi A, Calevo MG, Tamburrino F, Scarano E, Schiavariello C, Rossi C, Mazzanti L, Orlandini E, Pozzobon G, Finamore M, Baldoli C, Grandone A, Cirillo M, Aiello F, Corica D, Wasniewska M, Cattoni A, Remida P, Capalbo D, Tortora F, Salerno MC, Azzolini S, Mansour M, Faienza MF, Palladino S, Tortora D, Rosti G, Faravelli F, Venturino C, Capuozzo P, De Mori L, Maietta P, Allegri AEM, Morreale C, Angelelli A, Napoli F, Di Iorgi N, Rossi A, Maghnie M, Severino M.Patti G, et al.J Clin Endocrinol Metab. 2026 Aug 27:dgag352. doi: 10.1210/clinem/dgag352. Online ahead of print.J Clin Endocrinol Metab. 2026.PMID: 42657773 * [ Vesicoureteral Reflux. ](https://pubmed.ncbi.nlm.nih.gov/33085409/) Leslie SW, Aeddula NR.Leslie SW, et al.2024 Apr 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–.2024 Apr 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–.PMID: 33085409Free Books & Documents. * [ The Growth Characteristics of Patients with Noonan Syndrome: Results of Three Years of Growth Hormone Treatment: A Nationwide Multicenter Study. ](https://pubmed.ncbi.nlm.nih.gov/27125300/) Şıklar Z, Genens M, Poyrazoğlu Ş, Baş F, Darendeliler F, Bundak R, Aycan Z, Savaş Erdeve Ş, Çetinkaya S, Güven A, Abalı S, Atay Z, Turan S, Kara C, Can Yılmaz G, Akyürek N, Abacı A, Çelmeli G, Sarı E, Bolu S, Korkmaz HA, Şimşek E, Çatlı G, Büyükinan M, Çayır A, Evliyaoğlu O, İşgüven P, Özgen
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