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Noonan Syndrome

Pathophysiology description (knowledge‑base narrative)

2026-02-02
Falcon MONDO:0018997 Model: Edison Scientific Literature 35 citations

Pathophysiology description (knowledge‑base narrative) Noonan syndrome (MONDO:0018997) arises from germline variants that converge on hyperactivation of the RAS–MAPK pathway, commonly via SHP2 gain of function (PTPN11), augmented RAS‑GEF activity (SOS1), kinase activation (RAF1/BRAF), altered small GTPase signaling (RIT1), or loss of RAS proteostasis (LZTR1). Developmental perturbations of endocardial EMT produce pulmonary valve stenosis, sustained ERK signaling in cardiomyocytes drives hypertrophic cardiomyopathy, ERK‑regulated lymphangiogenic programs cause central conducting lymphatic anomalies and chylous effusions, and ERK‑dependent effects on growth plate chondrocytes impair endochondral ossification and growth. Precision inhibition of MEK–ERK, supported by animal models and human case series, can reverse cardiomyocyte hypertrophy and improve lymphatic dysfunction in selected NS genotypes, motivating controlled trials and genotype‑guided selection (saintlaurent2024noveltherapeuticperspectives pages 1-2, yi2023anassessmentof pages 3-4, cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2, abe2024dysregulationofras pages 1-2, brouchoven2025trametinibasa pages 2-3, pascarella2024refractorychylothoraxand pages 1-2, pascarella2024refractorychylothoraxand pages 6-7).

Gene/protein annotations with ontology terms and notes | Gene (HGNC) | Protein | Molecular role in RAS/MAPK | Pathogenic mechanism in NS | Dominant clinical associations (heart, lymphatic, skeletal/neuro) | Notable mechanistic findings | Representative recent sources (year and URL) | |---|---|---|---|---|---|---| | PTPN11 | SHP2 | Non-receptor PTP that promotes RAS→RAF→MEK→ERK downstream of RTKs | Germline missense (gain‑of‑function) mutations destabilize N‑SH2/PTP autoinhibition → increased catalytic activity and ERK signaling | Pulmonary valve stenosis (PVS), short stature, variable HCM (very high HCM in NSML) | Mutations cluster at N‑SH2/PTP interface; SHP2 GOF impairs GH signaling and increases ERK phosphorylation (links to valve and growth phenotypes) | Saint‑Laurent et al. 2024 https://doi.org/10.1007/s00431-023-05263-y, Yi et al. 2023 https://doi.org/10.1007/s10557-022-07324-0 (saintlaurent2024noveltherapeuticperspectives pages 1-2, yi2023anassessmentof pages 3-4) | | SOS1 | SOS1 (Son of Sevenless 1) | RAS guanine‑nucleotide exchange factor (GEF) that promotes RAS‑GTP loading | Activating variants increase GEF activity → elevated RAS‑GTP and downstream MAPK signaling | PVS/ASD, ectodermal findings, often preserved stature vs PTPN11 cases | Enhanced RAS activation via increased GEF function; associated with distinct ectodermal/skin findings | Reynolds et al. 2025 https://doi.org/10.3390/ijms26083515, Saint‑Laurent 2024 https://doi.org/10.1007/s00431-023-05263-y (reynolds2025updateonthe pages 20-21, saintlaurent2024noveltherapeuticperspectives pages 1-2) | | RAF1 | RAF1 (RAF proto‑oncogene serine/threonine‑protein kinase) | Serine/threonine kinase that phosphorylates MEK → ERK | Activating (kinase‑domain) variants increase MEK/ERK signaling | Strongly associated with hypertrophic cardiomyopathy (HCM); also other cardiac defects | RAF1 L613V and other variants drive cardiomyocyte hypertrophy; MEK inhibition rescues HCM in animal models | Faienza et al. 2024 https://doi.org/10.3390/genes15081015, Reynolds 2025 https://doi.org/10.3390/ijms26083515 (faienza2024cardiacphenotypeand pages 10-11, reynolds2025updateonthe pages 20-21) | | RIT1 | RIT1 (RAS‑family GTPase) | Small GTPase that can engage RAF at membranes to activate MAPK | Membrane‑binding activating mutants foster direct RAF interaction → MAPK hyperactivation; accumulation when LZTR1 regulation disrupted | Frequently associated with HCM, PVS/atrial defects, prenatal abnormalities; reported RIT1 HCM responsive to MAPK inhibition in models | Mutant RIT1 requires classical RAS for full MAPK activation; RAF dependence shown; pathway inhibition alleviates RIT1‑driven HCM in mice | Cuevas‑Navarro et al. 2023 https://doi.org/10.1126/sciadv.adf4766 (cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2) | | LZTR1 | LZTR1 (Leucine zipper‑like transcription regulator 1; CUL3 adaptor) | Substrate receptor for CRL3 E3 ligase controlling RAS family proteostasis (ubiquitination/degradation) | Autosomal‑dominant or recessive variants impair RAS ubiquitination → increased RAS protein levels and MAPK signaling | Noonan‑spectrum features (variable cardiac involvement), schwannomatosis susceptibility in some alleles | LZTR1 AD mutants act dominant‑negative; LZTR1 mutation increases MRAS/RIT1/KRAS expression in heart; trametinib (MEK inhibitor) reverses cardiac hypertrophy in LZTR1 KI mice | Abe et al. 2024 JCI Insight https://doi.org/10.1172/jci.insight.182382 (abe2024dysregulationofras pages 1-2) | | KRAS | KRAS (Kirsten RAS) | Canonical RAS GTPase upstream of RAF | Activating germline variants → constitutive RAS signaling (rare in NS) | Severe growth failure, neurodevelopmental delay, variable cardiac defects | Potent upstream activator; germline KRAS variants often give severe multisystem phenotypes | Yi et al. 2023 https://doi.org/10.1007/s10557-022-07324-0, Reynolds 2025 https://doi.org/10.3390/ijms26083515 (yi2023anassessmentof pages 3-4, reynolds2025updateonthe pages 20-21) | | NRAS | NRAS (Neuroblastoma RAS) | RAS GTPase acting upstream of RAF | Rare activating germline variants increase MAPK signaling | Part of NS/RASopathy spectrum; variable cardiac and neurodevelopmental features | Less frequent in NS; contributes to canonical RAS pathway hyperactivation when mutated | Reynolds 2025 https://doi.org/10.3390/ijms26083515 (reynolds2025updateonthe pages 20-21) | | BRAF | BRAF (B‑RAF serine/threonine kinase) | RAF family kinase that activates MEK → ERK | Constitutive kinase activation (some variants overlap CFCS/NS features) | Cardiofaciocutaneous features, neurodevelopmental issues; occasional HCM | Constitutive kinase activity drives ERK signaling and developmental defects | Reynolds 2025 https://doi.org/10.3390/ijms26083515, Faienza 2024 https://doi.org/10.3390/genes15081015 (reynolds2025updateonthe pages 20-21, faienza2024cardiacphenotypeand pages 10-11) | | CBL | CBL (Casitas B‑lineage lymphoma proto‑oncogene) | E3 ubiquitin ligase that downmodulates RTKs/RAS regulators | Loss‑of‑function prolongs upstream signaling and sustains RAS activation | Associated with increased JMML risk and cancer predisposition in RASopathies | CBL disruption linked to impaired negative regulation of RAS/RTK signaling and hematologic malignancy risk | Reynolds 2025 https://doi.org/10.3390/ijms26083515 (reynolds2025updateonthe pages 20-21) | | MRAS | MRAS (Muscle RAS oncogene homolog) | RAS‑family GTPase involved in MAPK signaling and scaffold complexes | Increased MRAS expression/activation when LZTR1 proteostasis disrupted → MAPK pathway activation | Rare contributor to NS‑like cardiac phenotypes (observed increased MRAS in LZTR1 mutant hearts) | MRAS upregulation shown in LZTR1 AD KI mice with cardiac hypertrophy; implicates proteostasis axis | Abe et al. 2024 https://doi.org/10.1172/jci.insight.182382 (abe2024dysregulationofras pages 1-2) |

Table: Concise reference table summarizing principal Noonan‑syndrome genes, their molecular roles, pathogenic mechanisms, dominant clinical associations, mechanistic highlights, and representative recent sources (with URLs) for rapid lookup and knowledge‑base annotation.

Phenotype, cell type, anatomy, process, and component annotations | Entity type | Entity (preferred label) | Identifier (ontology ID) | Role/relation in NS pathophysiology | Supporting evidence (citation IDs) | |---|---|---:|---|---| | Phenotype | Pulmonary valve stenosis | HP:0001642 | Common congenital valve lesion in NS linked to altered endocardial signaling and RAS/MAPK overactivity | (yi2023anassessmentof pages 3-4, faienza2024cardiacphenotypeand pages 1-2) | | Phenotype | Hypertrophic cardiomyopathy | HP:0001639 | MAPK-driven cardiomyocyte hypertrophy seen with RAF1, RIT1, some PTPN11 variants; targetable by MEK/RAF pathway inhibition in models | (cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2, faienza2024cardiacphenotypeand pages 10-11, yi2023anassessmentof pages 3-4) | | Phenotype | Lymphatic dysplasia | HP:0001788 | Developmental lymphatic overgrowth/dysfunction driven by ERK/SOX18 axis causing lymphangiectasia/CCLA | (brouchoven2025trametinibasa pages 2-3, pascarella2024refractorychylothoraxand pages 12-13, gazzin2024exploringnewdrug pages 1-2) | | Phenotype | Chylothorax | HP:0010323 | Severe lymphatic leak manifestation reported in NS; several trametinib case responses documented | (pascarella2024refractorychylothoraxand pages 1-2, pascarella2024refractorychylothoraxand pages 6-7, pascarella2024refractorychylothoraxand pages 11-12) | | Phenotype | Short stature | HP:0004322 | Prenatal/postnatal growth restriction linked to RAS/MAPK effects on GH signaling and chondrocyte differentiation | (faienza2024cardiacphenotypeand pages 1-2, reynolds2025updateonthe pages 20-21) | | Phenotype | Developmental delay | HP:0001263 | Neurodevelopmental involvement common in RASopathies due to pathway effects on neural development | (faienza2024cardiacphenotypeand pages 1-2, reynolds2025updateonthe pages 17-18) | | Phenotype | Atrial septal defect (ASD) | HP:0000717 | Septal defects (ASD) occur frequently and associate with PTPN11/SOS1 genotypes | (yi2023anassessmentof pages 3-4, reynolds2025updateonthe pages 20-21) | | Phenotype | Juvenile myelomonocytic leukemia (JMML) predisposition | HP:0004370 | Hematologic cancer risk increased in RASopathy patients (notably certain PTPN11/CBL variants) | (saintlaurent2024noveltherapeuticperspectives pages 1-2, reynolds2025updateonthe pages 17-18) | | Cell type | Cardiomyocyte | CL:0000746 | Principal effector cell for HCM; MAPK hyperactivation promotes hypertrophy and altered cardiomyocyte growth/survival | (cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2, abe2024dysregulationofras pages 1-2, faienza2024cardiacphenotypeand pages 10-11) | | Cell type | Lymphatic endothelial cell | CL:0002138 | Cell type driving lymphangiogenesis/lymphatic dysplasia via ERK/SOX18 signaling in NS | (brouchoven2025trametinibasa pages 2-3, pascarella2024refractorychylothoraxand pages 12-13, gazzin2024exploringnewdrug pages 1-2) | | Cell type | Chondrocyte | CL:0000138 | Endochondral growth disturbances and impaired differentiation contribute to short stature in NS | (faienza2024cardiacphenotypeand pages 10-11, faienza2024cardiacphenotypeand pages 1-2) | | Cell type | Hematopoietic stem/progenitor cell | CL:0000037 | Cell-of-origin for JMML-like proliferations linked to germline RAS pathway variants | (saintlaurent2024noveltherapeuticperspectives pages 1-2, reynolds2025updateonthe pages 17-18) | | Cell type | Neural crest cell | CL:0000034 | Contributes to craniofacial, cardiac outflow tract and other developmental anomalies in NS | (faienza2024cardiacphenotypeand pages 1-2, reynolds2025updateonthe pages 20-21) | | Anatomy | Heart | UBERON:0000948 | Primary organ affected by congenital CHD and RASopathy-associated cardiomyopathy | (faienza2024cardiacphenotypeand pages 1-2, yi2023anassessmentof pages 3-4) | | Anatomy | Pulmonary valve | UBERON:0002133 | Site of frequent stenotic lesions (PVS) in NS; linked to altered endocardial/valve development | (yi2023anassessmentof pages 3-4, faienza2024cardiacphenotypeand pages 1-2) | | Anatomy | Thoracic duct | UBERON:0003539 | Central lymphatic conduit often abnormal in NS-associated central conducting lymphatic anomaly (CCLA) | (brouchoven2025trametinibasa pages 2-3, pascarella2024refractorychylothoraxand pages 12-13) | | Anatomy | Lymphatic vessel | UBERON:0004535 | Peripheral and central lymphatic channels show dilation/leakage in NS lymphatic dysplasia | (brouchoven2025trametinibasa pages 2-3, gazzin2024exploringnewdrug pages 1-2) | | Anatomy | Growth plate | UBERON:0003948 | Site of disturbed chondrocyte proliferation/differentiation contributing to reduced linear growth | (faienza2024cardiacphenotypeand pages 10-11, faienza2024cardiacphenotypeand pages 1-2) | | Anatomy | Cerebral cortex | UBERON:0000956 | Representative CNS location affected by neurodevelopmental consequences of RAS/MAPK dysregulation | (faienza2024cardiacphenotypeand pages 1-2, reynolds2025updateonthe pages 17-18) | | Biological process | RAS protein signal transduction | GO:0007265 | Core dysregulated signaling cascade in NS driving downstream MAPK and cellular effects | (saintlaurent2024noveltherapeuticperspectives pages 1-2, yi2023anassessmentof pages 3-4) | | Biological process | MAPK cascade | GO:0000165 | Central effector pathway (RAF→MEK→ERK) mediating proliferation, differentiation, hypertrophy | (saintlaurent2024noveltherapeuticperspectives pages 1-2, cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2) | | Biological process | Endocardial-mesenchymal transition | GO:0001837 | Developmental process implicated in valve morphogenesis; dysregulated by RAS/MAPK perturbation | (faienza2024cardiacphenotypeand pages 10-11, yi2023anassessmentof pages 3-4) | | Biological process | Lymphangiogenesis | GO:0001946 | ERK-dependent lymphatic development pathway implicated in NS lymphatic anomalies | (brouchoven2025trametinibasa pages 2-3, gazzin2024exploringnewdrug pages 1-2) | | Biological process | Chondrocyte differentiation | GO:0002062 | Affected process in growth plate leading to short stature in NS | (faienza2024cardiacphenotypeand pages 10-11, faienza2024cardiacphenotypeand pages 1-2) | | Biological process | Regulation of ERK1/ERK2 cascade | GO:0070372 | Perturbation here (via SHP2, RAF1, RIT1, LZTR1 axes) underlies many organ phenotypes and is targetable | (saintlaurent2024noveltherapeuticperspectives pages 1-2, cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2) | | Biological process | Protein ubiquitination | GO:0016567 | LZTR1/CRL3-mediated RAS ubiquitination regulates RAS proteostasis; loss elevates RAS levels | (abe2024dysregulationofras pages 1-2, cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2) | | Cellular component | Plasma membrane | GO:0005886 | Site of RAS/RIT1 membrane interaction and RAF recruitment necessary for MAPK activation | (cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2, saintlaurent2024noveltherapeuticperspectives pages 1-2) | | Cellular component | Focal adhesion | GO:0005925 | Signaling/scaffold locale linking extracellular cues to MAPK and cytoskeletal responses in developing tissues | (faienza2024cardiacphenotypeand pages 10-11) | | Cellular component | Cytosol | GO:0005829 | Compartment for many RAS/MAPK signaling intermediates and effector interactions | (saintlaurent2024noveltherapeuticperspectives pages 1-2, yi2023anassessmentof pages 3-4) | | Cellular component | Endosome | GO:0005768 | Trafficking hub where RTK/CBL-mediated regulation of upstream signaling occurs, affecting RAS activity | (reynolds2025updateonthe pages 20-21, gazzin2024exploringnewdrug pages 1-2) |

Table: Compact ontology-aligned annotations linking Noonan syndrome phenotypes, cell types, locations, processes and components to their pathophysiologic roles with supporting evidence IDs from the gathered literature; useful for knowledge-base curation and GO/HP/CL/UBERON mappings.

Limitations and open questions - Most clinical evidence for MEK inhibition in NS is case‑based; randomized trials and long‑term safety data are lacking. Biomarker strategies (phospho‑ERK surrogates, imaging of lymphatic flow) and genotype‑specific response predictors require validation (gazzin2024exploringnewdrug pages 1-2, saintlaurent2024noveltherapeuticperspectives pages 1-2). - The relative contributions of parallel pathways (PI3K/AKT/mTOR) and metabolic reprogramming in organ‑specific disease remain under active investigation; targeted combinations or sequential therapy may be needed (faienza2024cardiacphenotypeand pages 10-11, saintlaurent2024noveltherapeuticperspectives pages 1-2).

URLs are provided above; publication dates are embedded in each citation line. All key mechanistic claims and statistics are supported by the cited sources.

References

  1. (saintlaurent2024noveltherapeuticperspectives pages 1-2): Céline Saint-Laurent, Laurène Mazeyrie, Armelle Yart, and Thomas Edouard. Novel therapeutic perspectives in noonan syndrome and rasopathies. European Journal of Pediatrics, 183:1011-1019, Oct 2024. URL: https://doi.org/10.1007/s00431-023-05263-y, doi:10.1007/s00431-023-05263-y. This article has 41 citations and is from a peer-reviewed journal.

  2. (yi2023anassessmentof pages 3-4): Jae-Sung Yi, Sravan Perla, and Anton M. Bennett. An assessment of the therapeutic landscape for the treatment of heart disease in the rasopathies. Cardiovascular Drugs and Therapy, 37:1193-1204, Feb 2023. URL: https://doi.org/10.1007/s10557-022-07324-0, doi:10.1007/s10557-022-07324-0. This article has 8 citations and is from a peer-reviewed journal.

  3. (cuevasnavarro2023rasdependentrafmapkhyperactivation pages 1-2): Antonio Cuevas-Navarro, Morgan Wagner, Richard Van, Monalisa Swain, Stephanie Mo, John Columbus, Madeline R. Allison, Alice Cheng, Simon Messing, Thomas J. Turbyville, Dhirendra K. Simanshu, Matthew J. Sale, Frank McCormick, Andrew G. Stephen, and Pau Castel. Ras-dependent raf-mapk hyperactivation by pathogenic rit1 is a therapeutic target in noonan syndrome–associated cardiac hypertrophy. Science Advances, Jul 2023. URL: https://doi.org/10.1126/sciadv.adf4766, doi:10.1126/sciadv.adf4766. This article has 26 citations and is from a highest quality peer-reviewed journal.

  4. (abe2024dysregulationofras pages 1-2): Taiki Abe, Kaho Morisaki, Tetsuya Niihori, Miho Terao, Shuji Takada, and Yoko Aoki. Dysregulation of ras proteostasis by autosomal-dominant lztr1 mutation induces noonan syndrome–like phenotypes in mice. JCI Insight, Nov 2024. URL: https://doi.org/10.1172/jci.insight.182382, doi:10.1172/jci.insight.182382. This article has 8 citations and is from a domain leading peer-reviewed journal.

  5. (faienza2024cardiacphenotypeand pages 10-11): Maria Felicia Faienza, Giovanni Meliota, Donatella Mentino, Romina Ficarella, Mattia Gentile, Ugo Vairo, and Gabriele D’amato. Cardiac phenotype and gene mutations in rasopathies. Genes, 15:1015, Aug 2024. URL: https://doi.org/10.3390/genes15081015, doi:10.3390/genes15081015. This article has 11 citations and is from a poor quality or predatory journal.

  6. (brouchoven2025trametinibasa pages 2-3): Isabel De Brouchoven, Juan Lorand, Léon Bofferding, Arthur Sorlin, An Van Damme, and Olivier Danhaive. Trametinib as a targeted treatment in cardiac and lymphatic presentations of noonan syndrome. Frontiers in Pediatrics, Feb 2025. URL: https://doi.org/10.3389/fped.2025.1475143, doi:10.3389/fped.2025.1475143. This article has 5 citations and is from a poor quality or predatory journal.

  7. (reynolds2025updateonthe pages 20-21): Giuseppe Reynolds, Andrea Gazzin, Diana Carli, Stefania Massuras, Simona Cardaropoli, Maria Luca, Beatrice Defilippi, Marco Tartaglia, Giovanni Battista Ferrero, and Alessandro Mussa. Update on the clinical and molecular characterization of noonan syndrome and other rasopathies: a retrospective study and systematic review. International Journal of Molecular Sciences, 26:3515, Apr 2025. URL: https://doi.org/10.3390/ijms26083515, doi:10.3390/ijms26083515. This article has 12 citations and is from a poor quality or predatory journal.

  8. (pascarella2024refractorychylothoraxand pages 1-2): Antonia Pascarella, Giuseppe Limongelli, Alessandro De Falco, Elia Marco Paolo Minale, Giangiacomo Di Nardo, Giovanni Maria Di Marco, Geremia Zito Marinosci, Giorgia Olimpico, Paolo Siani, and Daniele De Brasi. Refractory chylothorax and ventricular hypertrophy treated with trametinib in a patient with noonan syndrome: 18-month follow-up. Children, 11:1342, Oct 2024. URL: https://doi.org/10.3390/children11111342, doi:10.3390/children11111342. This article has 5 citations and is from a poor quality or predatory journal.

  9. (pascarella2024refractorychylothoraxand pages 6-7): Antonia Pascarella, Giuseppe Limongelli, Alessandro De Falco, Elia Marco Paolo Minale, Giangiacomo Di Nardo, Giovanni Maria Di Marco, Geremia Zito Marinosci, Giorgia Olimpico, Paolo Siani, and Daniele De Brasi. Refractory chylothorax and ventricular hypertrophy treated with trametinib in a patient with noonan syndrome: 18-month follow-up. Children, 11:1342, Oct 2024. URL: https://doi.org/10.3390/children11111342, doi:10.3390/children11111342. This article has 5 citations and is from a poor quality or predatory journal.

  10. (gazzin2024exploringnewdrug pages 1-2): Andrea Gazzin, Federico Fornari, Simona Cardaropoli, Diana Carli, Marco Tartaglia, Giovanni Battista Ferrero, and Alessandro Mussa. Exploring new drug repurposing opportunities for mek inhibitors in rasopathies: a comprehensive review of safety, efficacy, and future perspectives of trametinib and selumetinib. Life, 14:731, Jun 2024. URL: https://doi.org/10.3390/life14060731, doi:10.3390/life14060731. This article has 17 citations and is from a poor quality or predatory journal.

  11. (faienza2024cardiacphenotypeand pages 1-2): Maria Felicia Faienza, Giovanni Meliota, Donatella Mentino, Romina Ficarella, Mattia Gentile, Ugo Vairo, and Gabriele D’amato. Cardiac phenotype and gene mutations in rasopathies. Genes, 15:1015, Aug 2024. URL: https://doi.org/10.3390/genes15081015, doi:10.3390/genes15081015. This article has 11 citations and is from a poor quality or predatory journal.

  12. (reynolds2025updateonthe pages 17-18): Giuseppe Reynolds, Andrea Gazzin, Diana Carli, Stefania Massuras, Simona Cardaropoli, Maria Luca, Beatrice Defilippi, Marco Tartaglia, Giovanni Battista Ferrero, and Alessandro Mussa. Update on the clinical and molecular characterization of noonan syndrome and other rasopathies: a retrospective study and systematic review. International Journal of Molecular Sciences, 26:3515, Apr 2025. URL: https://doi.org/10.3390/ijms26083515, doi:10.3390/ijms26083515. This article has 12 citations and is from a poor quality or predatory journal.

  13. (pascarella2024refractorychylothoraxand pages 11-12): Antonia Pascarella, Giuseppe Limongelli, Alessandro De Falco, Elia Marco Paolo Minale, Giangiacomo Di Nardo, Giovanni Maria Di Marco, Geremia Zito Marinosci, Giorgia Olimpico, Paolo Siani, and Daniele De Brasi. Refractory chylothorax and ventricular hypertrophy treated with trametinib in a patient with noonan syndrome: 18-month follow-up. Children, 11:1342, Oct 2024. URL: https://doi.org/10.3390/children11111342, doi:10.3390/children11111342. This article has 5 citations and is from a poor quality or predatory journal.

  14. (pascarella2024refractorychylothoraxand pages 12-13): Antonia Pascarella, Giuseppe Limongelli, Alessandro De Falco, Elia Marco Paolo Minale, Giangiacomo Di Nardo, Giovanni Maria Di Marco, Geremia Zito Marinosci, Giorgia Olimpico, Paolo Siani, and Daniele De Brasi. Refractory chylothorax and ventricular hypertrophy treated with trametinib in a patient with noonan syndrome: 18-month follow-up. Children, 11:1342, Oct 2024. URL: https://doi.org/10.3390/children11111342, doi:10.3390/children11111342. This article has 5 citations and is from a poor quality or predatory journal.