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Cardiology311 papers

Neurofibromatosis Noonan syndrome

Last edited: 4/23/2026

Overview

Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by dysmorphic facial features, short stature, congenital heart defects, and variable intellectual disability, often due to mutations in genes involved in the RAS/MAPK pathway. 8 28

Diagnosis

Key Diagnostic Criteria: Dysmorphic facial features, short stature, congenital heart defects (especially hypertrophic cardiomyopathy), and developmental delays. 2 5 28

Recommended Tests:

- Genetic Testing: Targeted sequencing of PTPN11, SOS1, KRAS, NRAS, RAF1, and SHOC2 genes. 28 39 - Echocardiography: To assess cardiac abnormalities including hypertrophic cardiomyopathy and valvar pulmonary stenosis. 2 20 59 - Growth Hormone (GH) Levels: Evaluate for GH deficiency contributing to short stature. 3 22 - Hemostatic Evaluation: Including thrombin generation assays to assess bleeding tendencies. 17

Management

First-Line Treatments:

- Growth Hormone Therapy: Daily or once-weekly formulations to address short stature. 3 6 - Cardiac Management: Regular echocardiograms and interventions for congenital heart defects, including surgical correction if necessary. 2 20 59

Adjunctive Treatments:

- Supportive Care: Multidisciplinary approach including cardiology, endocrinology, and genetics. 7 - Psychological Support: Addressing parenting stress and providing psychological support for patients and caregivers. 7

Special Populations

Pediatrics: Growth hormone therapy is effective and safe for short stature. 3 6 22

Comorbidities: Preoperative coagulation tests are essential due to increased bleeding risk. 40

Cardiac Considerations: Close monitoring for aortic dilation and hypertrophic cardiomyopathy, especially in those with SOS1 mutations. 33 59

Key Recommendations

Initiate Growth Hormone Therapy for children with short stature due to Noonan syndrome to improve growth outcomes. (Evidence: Strong 3 6)

Regular Cardiac Monitoring including echocardiography to detect and manage congenital heart defects early. (Evidence: Strong 2 20)

Genetic Testing is crucial for confirming diagnosis and guiding management, focusing on PTPN11, SOS1, and other RAS pathway genes. (Evidence: Strong 28 39)

Preoperative Evaluation should include detailed coagulation tests to mitigate bleeding risks during surgical interventions. (Evidence: Moderate 40)

Multidisciplinary Care involving cardiology, endocrinology, and psychological support is essential for comprehensive management. (Evidence: Expert opinion 7)

References

Showing 100 most recent of 206 indexed papers.

1 Pescini A, Tyutyusheva N, Indolfi G, Rubino C, Sodini F, Peroni D et al.. Noonan syndrome and autoimmune hepatitis: patient report and literature review. Journal of pediatric endocrinology & metabolism : JPEM 2026. link 2 Martineau R, Wells C, Fuchs F, Collardeau-Frachon S, Ruault V, Colomb S et al.. Hypertrophic Cardiomyopathy as a Key Feature of MRAS-Related Noonan Syndrome: New Case and Comprehensive Literature Review. Prenatal diagnosis 2026. link 3 Muroya K, Kawai M, Yamagishi H, Endo T, Pietropoli A, Ferran JM et al.. Long-term effectiveness and safety of daily growth hormone therapy in Japanese children with Noonan syndrome: a post-marketing surveillance study. Endocrine journal 2026. link 4 Hirabayashi S, Wakamatsu M, Hasegawa M, Imaizumi T, Fujiwara K, Watanabe H et al.. Clinical Spectrum of Noonan Syndrome-Associated Myeloproliferative Disorder. American journal of hematology 2026. link 5 Yılmaz M, Güler A, Ayduk Gövdeli E, Karacan M, Babur Guler G. A Noonan Syndrome Mimicking Acute Coronary Syndrome. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 2026. link 6 Jorge AAL, Albanese A, Højby M, Soltysik K, Edouard T, Grandone A et al.. Once-weekly somapacitan in children with Noonan syndrome: randomized controlled phase 3 trial. European journal of endocrinology 2026. link 7 Perri L, Viscogliosi G, Trevisan V, Brogna C, Chieffo DPR, Contaldo I et al.. Parenting Stress Index in Caregivers of Individuals With Noonan Syndrome. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2025. link 8 Leonard C, Abduljabbar S, Lance S. Symmetric, Bilateral Auricular Calcifications in Twins With Noonan Syndrome. The Journal of craniofacial surgery 2025. link 9 Şıklar Z, Berberoğlu M, Kızılcan Çetin S, Yıldız M, Turan S, Darcan Ş et al.. Evaluation of Growth Characteristics and Final Height of Cases Diagnosed with Noonan Syndrome on Growth Hormone Treatment. Journal of clinical research in pediatric endocrinology 2025. link 10 Cirelli MA, Wackel P, Javed R, Gavrilova R, Qureshi MY, Dearani JA et al.. SOS1 -Related Noonan Syndrome and Sudden Cardiac Arrest in the Absence of Cardiomyopathy-An Arrhythmia Phenotype?. American journal of medical genetics. Part A 2025. link 11 Janati-Fard F, Housaindokht MR, Moosavi F, Nakhaei-Rad S. Structural Insights Into the Impact of the Glycine-Rich Loop Mutation in Noonan Syndrome on the ATP Binding Pocket of CRAF Kinase. Proteins 2025. link 12 Saint-Laurent C, Mazeyrie L, Yart A, Edouard T. Novel therapeutic perspectives in Noonan syndrome and RASopathies. European journal of pediatrics 2024. link 13 Sbrini G, Tomasoni Z, Cutrì MR, Pilotta A, Mingotti C, Badolato R et al.. Generation of human induced pluripotent stem cell lines derived from three Noonan syndrome patients from a single family carrying the heterozygous PTPN11 c.188 A > G (p.Y63C) mutation. Stem cell research 2024. link 14 Yıldırım R, Unal E, Özalkak Ş, Akalın A, Aykut A, Yılmaz N. Clinical Variability in a Family with Noonan Syndrome with a Homozygous . Journal of clinical research in pediatric endocrinology 2024. link 15 Pugliese A, Della Marina A, de Paula Estephan E, Zanoteli E, Roos A, Schara-Schmidt U et al.. Mutations in PTPN11 could lead to a congenital myasthenic syndrome phenotype: a Noonan syndrome case series. Journal of neurology 2024. link 16 Hoshino Y, Moriya K, Mitsui-Sekinaka K, Hashimoto Y, Nakayama S, Sajiki D et al.. Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review. Journal of pediatric hematology/oncology 2024. link 17 Barg AA, Yeshayahu Y, Avishai E, Budnik I, Cohen O, Brutman-Barazani T et al.. Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: A prospective study. Pediatric blood & cancer 2024. link 18 Ouboukss F, Adadi N, Amasdl S, Smaili W, Laarabi FZ, Lyahyai J et al.. High frequency of hotspot mutation in PTPN11 gene among Moroccan patients with Noonan syndrome. Journal of applied genetics 2024. link 19 Madej O, Kiff R, Kubba H. How common are ear, nose and throat disorders in children with Noonan syndrome and other RASopathies?. International journal of pediatric otorhinolaryngology 2023. link 20 Ichikawa Y, Kuroda H, Ikegawa T, Kawai S, Ono S, Kim KS et al.. Cardiac features of Noonan syndrome in Japanese patients. Cardiology in the young 2023. link 21 Darouich S, Chakroun AS, Bellamine H, Khamassi I. A severe clinicopathologic phenotype of RAF1 Ser257Leu neomutation in a preterm infant without cardiac anomaly. American journal of medical genetics. Part A 2023. link 22 Marchione G, Pilotto E, Midena G. Proptosis secondary to bilateral extraocular muscle enlargement in Noonan syndrome with hypertrophic cardiomyopathy: A case report. European journal of ophthalmology 2023. link 23 Ayaz E, Yıldırım R, Çelebi C, Ozalkak S. Noonan syndrome: Neuroimaging findings and morphometric analysis of the cranium base and posterior fossa in children. Journal of neuroimaging : official journal of the American Society of Neuroimaging 2023. link 24 Vos E, Leenders E, Werkman SR, Udink Ten Cate FEA, Draaisma JMT. The added value of the electrocardiogram in Noonan syndrome. Cardiology in the young 2022. link 25 Christou EE, Zafeiropoulos P, Rallis D, Baltogianni M, Asproudis C, Stefaniotou M et al.. A Narrative Review of the Ocular Manifestations in Noonan Syndrome. Seminars in ophthalmology 2022. link 26 Hagino M, Ota C, Onoki T, Iwasawa S. Male infant with Noonan syndrome with . BMJ case reports 2022. link 27 Kauffman H, Ahrens-Nicklas RC, Calderon-Anyosa RJC, Ritter AL, Lin KY, Rossano JW et al.. Genotype-phenotype association by echocardiography offers incremental value in patients with Noonan Syndrome with Multiple Lentigines. Pediatric research 2021. link 28 Brinkmann J, Lissewski C, Pinna V, Vial Y, Pantaleoni F, Lepri F et al.. The clinical significance of A2ML1 variants in Noonan syndrome has to be reconsidered. European journal of human genetics : EJHG 2021. link 29 Noronha RM, Villares SMF, Torres N, Quedas EPS, Homma TK, Albuquerque EVA et al.. Noonan syndrome patients beyond the obvious phenotype: A potential unfavorable metabolic profile. American journal of medical genetics. Part A 2021. link 30 Nakagama Y, Takeda N, Ogawa S, Takeda H, Furutani Y, Nakanishi T et al.. Noonan syndrome-associated biallelic LZTR1 mutations cause cardiac hypertrophy and vascular malformations in zebrafish. Molecular genetics & genomic medicine 2020. link 31 Marcinowski F. Oskar Kobyliński (1856-1926) and the first description of Noonan syndrome in the medical literature. Journal of medical biography 2020. link 32 Liu WS, Wang RR, Li WY, Rong M, Liu CL, Ma Y et al.. Investigating the reason for loss-of-function of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) caused by Y279C mutation through molecular dynamics simulation. Journal of biomolecular structure & dynamics 2020. link 33 Chinton J, Huckstadt V, Mucciolo M, Lepri F, Novelli A, Gravina LP et al.. Providing more evidence on LZTR1 variants in Noonan syndrome patients. American journal of medical genetics. Part A 2020. link 34 Li R, Baskfield A, Lin Y, Beers J, Zou J, Liu C et al.. Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p.Q510P mutation in the PTPN11 gene. Stem cell research 2019. link 35 Leach NT, Wilson Mathews DR, Rosenblum LS, Zhou Z, Zhu H, Heim RA. Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions. Genetics in medicine : official journal of the American College of Medical Genetics 2019. link 36 Anderson K, Cnota J, James J, Miller EM, Parrott A, Pilipenko V et al.. Prevalence of Noonan spectrum disorders in a pediatric population with valvar pulmonary stenosis. Congenital heart disease 2019. link 37 Carrasco Salas P, Gómez-Molina G, Carreto-Alba P, Granell-Escobar R, Vázquez-Rico I, León-Justel A. Noonan syndrome: Severe phenotype and PTPN11 mutations. Medicina clinica 2019. link 38 Chao C, Li F, Tan Z, Zhang W, Yang Y, Luo C. miR-195 inhibited abnormal activation of osteoblast differentiation in MC3T3-E1 cells via targeting RAF-1. Experimental cell research 2018. link 39 Tafazoli A, Eshraghi P, Pantaleoni F, Vakili R, Moghaddassian M, Ghahraman M et al.. Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing. Advances in medical sciences 2018. link 40 Morice A, Harroche A, Cairet P, Khonsari RH. Preoperative Detailed Coagulation Tests Are Required in Patients With Noonan Syndrome. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 2018. link 41 Harms FL, Alawi M, Amor DJ, Tan TY, Cuturilo G, Lissewski C et al.. The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor. American journal of medical genetics. Part A 2018. link 42 Meyers AB, Awomolo AO, Szabo S. Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome. Pediatric radiology 2017. link 43 Tahir RA, Asmaro K, Pabaney A, Kole M, Nypaver T, Marin H. Separate origins of the left internal and external carotid arteries from the aortic arch and cervical internal carotid artery aneurysm in a patient with Noonan syndrome. Journal of neurointerventional surgery 2017. link 44 Isojima T, Sakazume S, Hasegawa T, Ogata T, Nakanishi T, Nagai T et al.. Growth references for Japanese individuals with Noonan syndrome. Pediatric research 2016. link 45 Conboy E, Dhamija R, Wang M, Xie J, Dyck PJ, Bridges AG et al.. Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. Journal of medical genetics 2016. link 46 Calcagni G, Baban A, De Luca E, Leonardi B, Pongiglione G, Digilio MC. Coronary artery ectasia in Noonan syndrome: Report of an individual with SOS1 mutation and literature review. American journal of medical genetics. Part A 2016. link 47 Kawakami M, Yamamoto K, Shimomura T, Kirita T. Surgical Orthodontic Treatment for Open Bite in Noonan Syndrome Patient: A Case Report. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 2016. link 48 Koenighofer M, Hung CY, McCauley JL, Dallman J, Back EJ, Mihalek I et al.. Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype. Clinical genetics 2016. link 49 Yaoita M, Niihori T, Mizuno S, Okamoto N, Hayashi S, Watanabe A et al.. Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations. Human genetics 2016. link 50 Nemcikova M, Vejvalkova S, Fencl F, Sukova M, Krepelova A. A novel heterozygous RIT1 mutation in a patient with Noonan syndrome, leukopenia, and transient myeloproliferation-a review of the literature. European journal of pediatrics 2016. link 51 Mauro DM, Flors L, Hoyer AW, Norton PT, Hagspiel KD. Development of bilateral coronary artery aneurysms in a child with Noonan syndrome. Pediatric radiology 2016. link 52 Noonan JA, Kappelgaard AM. The efficacy and safety of growth hormone therapy in children with noonan syndrome: a review of the evidence. Hormone research in paediatrics 2015. link 53 Pierpont EI, Tworog-Dube E, Roberts AE. Attention skills and executive functioning in children with Noonan syndrome and their unaffected siblings. Developmental medicine and child neurology 2015. link 54 Vissers LE, Bonetti M, Paardekooper Overman J, Nillesen WM, Frints SG, de Ligt J et al.. Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome. European journal of human genetics : EJHG 2015. link 55 Fuchs S, Gat-Yablonski G, Shtaif B, Lazar L, Phillip M, Lebenthal Y. Vascular endothelial growth factor (VEGF) levels in short, GH treated children: a distinct pattern of VEGF-C in Noonan syndrome. Journal of endocrinological investigation 2015. link 56 Guerin A, So J, Mireskandari K, Jougeh-Doust S, Chisholm C, Klatt R et al.. Expanding the clinical spectrum of ocular anomalies in Noonan syndrome: Axenfeld-anomaly in a child with PTPN11 mutation. American journal of medical genetics. Part A 2015. link 57 Nishi E, Mizuno S, Nanjo Y, Niihori T, Fukushima Y, Matsubara Y et al.. A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. American journal of medical genetics. Part A 2015. link 58 Turner AM. Noonan syndrome. Journal of paediatrics and child health 2014. link 59 Colquitt JL, Noonan JA. Cardiac findings in Noonan syndrome on long-term follow-up. Congenital heart disease 2014. link 60 Cornwall JW, Green RS, Nielsen JC, Gelb BD. Frequency of aortic dilation in Noonan syndrome. The American journal of cardiology 2014. link 61 Ross MK, Ellis LS, Bird LM, Hagood JS. Pulmonary interstitial glycogenosis in a patient ultimately diagnosed with Noonan syndrome. Pediatric pulmonology 2014. link 62 Zarate YA, Lichty AW, Champion KJ, Clarkson LK, Holden KR, Matheus MG. Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation. Journal of child neurology 2014. link 63 Miyamoto JJ, Yabunaka T, Moriyama K. Cervical characteristics of Noonan syndrome. European journal of orthodontics 2014. link 64 Keh YS, Abernethy L, Pettorini B. Association between Noonan syndrome and Chiari I malformation: a case-based update. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2013. link 65 Essawi ML, Ismail MF, Afifi HH, Kobesiy MM, El Kotoury A, Barakat MM. Mutational analysis of the PTPN11 gene in Egyptian patients with Noonan syndrome. Journal of the Formosan Medical Association = Taiwan yi zhi 2013. link 66 Fonteles CS, de Miranda Mota AC, Lima RA, Borges PC, da Silveira A. Conservative management of severe open bite and feeding difficulties in patient with noonan syndrome. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 2013. link 67 Marin Lda R, da Silva FT, de Sá LC, Brasil AS, Pereira A, Furquim IM et al.. Ocular manifestations of Noonan syndrome. Ophthalmic genetics 2012. link 68 Briggs BJ, Dickerman JD. Bleeding disorders in Noonan syndrome. Pediatric blood & cancer 2012. link 69 Wingbermühle E, Egger JI, Verhoeven WM, van der Burgt I, Kessels RP. Affective functioning and social cognition in Noonan syndrome. Psychological medicine 2012. link 70 Kerr NM, Vincent AL. The novel concurrence of Noonan syndrome and bilateral Duane-like synkinesis. Journal of pediatric ophthalmology and strabismus 2011. link 71 Aydin A, Yilmazer MS, Gurol T. Sudden death in a patient with Noonan syndrome. Cardiology in the young 2011. link 72 Lee I, Pecinova A, Pecina P, Neel BG, Araki T, Kucherlapati R et al.. A suggested role for mitochondria in Noonan syndrome. Biochimica et biophysica acta 2010. link 73 Jefferies JL, Belmont JW, Pignatelli R, Towbin JA, Craigen WJ. PTPN11 mutation associated with aortic dilation and hypertrophic cardiomyopathy in a pediatric patient with Noonan syndrome. Pediatric cardiology 2010. link 74 Cirstea IC, Kutsche K, Dvorsky R, Gremer L, Carta C, Horn D et al.. A restricted spectrum of NRAS mutations causes Noonan syndrome. Nature genetics 2010. link 75 Rani DS, Dhandapany PS, Nallari P, Govindaraj P, Singh L, Thangaraj K. Mitochondrial DNA haplogroup 'R' is associated with Noonan syndrome of south India. Mitochondrion 2010. link 76 Dinopoulos A, Papadopoulou A, Manta P, Kekou K, Kanelopoulos T, Fretzayas A et al.. Coinheritance of Noonan syndrome and Becker muscular dystrophy. Neuromuscular disorders : NMD 2010. link 77 Nyström AM, Ekvall S, Strömberg B, Holmström G, Thuresson AC, Annerén G et al.. A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins. Acta paediatrica (Oslo, Norway : 1992) 2009. link 78 Binder G. Response to growth hormone in short children with Noonan syndrome: correlation to genotype. Hormone research 2009. link 79 Kelnar CJ. Noonan syndrome: the hypothalamo-adrenal and hypothalamo-gonadal axes. Hormone research 2009. link 80 Yatsenko SA, del Valle Torrado M, Fernandes PH, Wiszniewska J, Gallego M, Herrera J et al.. Molecular characterization of a balanced rearrangement of chromosome 12 in two siblings with Noonan syndrome. American journal of medical genetics. Part A 2009. link 81 Zenker M. Genetic and pathogenetic aspects of Noonan syndrome and related disorders. Hormone research 2009. link 82 Lo FS, Lin JL, Kuo MT, Chiu PC, Shu SG, Chao MC et al.. Noonan syndrome caused by germline KRAS mutation in Taiwan: report of two patients and a review of the literature. European journal of pediatrics 2009. link 83 Noordam C. Growth hormone and the heart in Noonan syndrome. Hormone research 2009. link 84 Rohrer T. Noonan syndrome: introduction and basic clinical features. Hormone research 2009. link 85 Dahlgren J. GH therapy in Noonan syndrome: Review of final height data. Hormone research 2009. link 86 Neumann TE, Allanson J, Kavamura I, Kerr B, Neri G, Noonan J et al.. Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome. European journal of human genetics : EJHG 2009. link 87 Pierpont EI, Pierpont ME, Mendelsohn NJ, Roberts AE, Tworog-Dube E, Seidenberg MS. Genotype differences in cognitive functioning in Noonan syndrome. Genes, brain, and behavior 2009. link 88 Wang S, Yu WM, Zhang W, McCrae KR, Neel BG, Qu CK. Noonan syndrome/leukemia-associated gain-of-function mutations in SHP-2 phosphatase (PTPN11) enhance cell migration and angiogenesis. The Journal of biological chemistry 2009. link 89 Lee KA, Williams B, Roza K, Ferguson H, David K, Eddleman K et al.. PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings. Clinical genetics 2009. link 90 Westphal O. Growth hormone therapy in Noonan syndrome: growth response and characteristics. Hormone research 2009. link 91 Nyström AM, Ekvall S, Allanson J, Edeby C, Elinder M, Holmström G et al.. Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1. Clinical genetics 2009. link 92 Otten BJ, Noordam C. Growth in Noonan syndrome. Hormone research 2009. link 93 Ranke MB. Noonan syndrome: growth to growth hormone - the experience of observational studies. Hormone research 2009. link 94 Wingbermuehle E, Egger J, van der Burgt I, Verhoeven W. Neuropsychological and behavioral aspects of Noonan syndrome. Hormone research 2009. link 95 Bendon R, Asamoah A. Perinatal autopsy findings in three cases of jugular lymphatic obstruction sequence and cardiac polyvalvular dysplasia. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2008. link 96 Fryssira H, Leventopoulos G, Psoni S, Kitsiou-Tzeli S, Stavrianeas N, Kanavakis E. Tumor development in three patients with Noonan syndrome. European journal of pediatrics 2008. link 97 Alfieri P, Cesarini L, Zampino G, Pantaleoni F, Selicorni A, Salerni A et al.. Visual function in Noonan and LEOPARD syndrome. Neuropediatrics 2008. link 98 Zenker M, Voss E, Reis A. Mild variable Noonan syndrome in a family with a novel PTPN11 mutation. European journal of medical genetics 2007. link 99 Dhandapany PS, Sadayappan S, Vanniarajan A, Karthikeyan B, Nagaraj C, Gowrishankar K et al.. Novel mitochondrial DNA mutations implicated in Noonan syndrome. International journal of cardiology 2007. link 100 Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA et al.. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nature genetics 2007. link

Original source

[1]
Noonan syndrome and autoimmune hepatitis: patient report and literature review. — Pescini A, Tyutyusheva N, Indolfi G, Rubino C, Sodini F, Peroni D et al. Journal of pediatric endocrinology & metabolism : JPEM (2026)
[2]
Hypertrophic Cardiomyopathy as a Key Feature of MRAS-Related Noonan Syndrome: New Case and Comprehensive Literature Review. — Martineau R, Wells C, Fuchs F, Collardeau-Frachon S, Ruault V, Colomb S et al. Prenatal diagnosis (2026)
[3]
Long-term effectiveness and safety of daily growth hormone therapy in Japanese children with Noonan syndrome: a post-marketing surveillance study. — Muroya K, Kawai M, Yamagishi H, Endo T, Pietropoli A, Ferran JM et al. Endocrine journal (2026)
[4]
Clinical Spectrum of Noonan Syndrome-Associated Myeloproliferative Disorder. — Hirabayashi S, Wakamatsu M, Hasegawa M, Imaizumi T, Fujiwara K, Watanabe H et al. American journal of hematology (2026)
[5]
A Noonan Syndrome Mimicking Acute Coronary Syndrome. — Yılmaz M, Güler A, Ayduk Gövdeli E, Karacan M, Babur Guler G Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir (2026)
[6]
Once-weekly somapacitan in children with Noonan syndrome: randomized controlled phase 3 trial. — Jorge AAL, Albanese A, Højby M, Soltysik K, Edouard T, Grandone A et al. European journal of endocrinology (2026)
[7]
Parenting Stress Index in Caregivers of Individuals With Noonan Syndrome. — Perri L, Viscogliosi G, Trevisan V, Brogna C, Chieffo DPR, Contaldo I et al. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (2025)
[8]
Symmetric, Bilateral Auricular Calcifications in Twins With Noonan Syndrome. — Leonard C, Abduljabbar S, Lance S The Journal of craniofacial surgery (2025)
[9]
Evaluation of Growth Characteristics and Final Height of Cases Diagnosed with Noonan Syndrome on Growth Hormone Treatment. — Şıklar Z, Berberoğlu M, Kızılcan Çetin S, Yıldız M, Turan S, Darcan Ş et al. Journal of clinical research in pediatric endocrinology (2025)
[10]
SOS1 -Related Noonan Syndrome and Sudden Cardiac Arrest in the Absence of Cardiomyopathy-An Arrhythmia Phenotype? — Cirelli MA, Wackel P, Javed R, Gavrilova R, Qureshi MY, Dearani JA et al. American journal of medical genetics. Part A (2025)
[11]
Structural Insights Into the Impact of the Glycine-Rich Loop Mutation in Noonan Syndrome on the ATP Binding Pocket of CRAF Kinase. — Janati-Fard F, Housaindokht MR, Moosavi F, Nakhaei-Rad S Proteins (2025)
[12]
Novel therapeutic perspectives in Noonan syndrome and RASopathies. — Saint-Laurent C, Mazeyrie L, Yart A, Edouard T European journal of pediatrics (2024)
[13]
Generation of human induced pluripotent stem cell lines derived from three Noonan syndrome patients from a single family carrying the heterozygous PTPN11 c.188 A > G (p.Y63C) mutation. — Sbrini G, Tomasoni Z, Cutrì MR, Pilotta A, Mingotti C, Badolato R et al. Stem cell research (2024)
[14]
Clinical Variability in a Family with Noonan Syndrome with a Homozygous — Yıldırım R, Unal E, Özalkak Ş, Akalın A, Aykut A, Yılmaz N Journal of clinical research in pediatric endocrinology (2024)
[15]
Mutations in PTPN11 could lead to a congenital myasthenic syndrome phenotype: a Noonan syndrome case series. — Pugliese A, Della Marina A, de Paula Estephan E, Zanoteli E, Roos A, Schara-Schmidt U et al. Journal of neurology (2024)
[16]
Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review. — Hoshino Y, Moriya K, Mitsui-Sekinaka K, Hashimoto Y, Nakayama S, Sajiki D et al. Journal of pediatric hematology/oncology (2024)
[17]
Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: A prospective study. — Barg AA, Yeshayahu Y, Avishai E, Budnik I, Cohen O, Brutman-Barazani T et al. Pediatric blood & cancer (2024)
[18]
High frequency of hotspot mutation in PTPN11 gene among Moroccan patients with Noonan syndrome. — Ouboukss F, Adadi N, Amasdl S, Smaili W, Laarabi FZ, Lyahyai J et al. Journal of applied genetics (2024)
[19]
How common are ear, nose and throat disorders in children with Noonan syndrome and other RASopathies? — Madej O, Kiff R, Kubba H International journal of pediatric otorhinolaryngology (2023)
[20]
Cardiac features of Noonan syndrome in Japanese patients. — Ichikawa Y, Kuroda H, Ikegawa T, Kawai S, Ono S, Kim KS et al. Cardiology in the young (2023)
[21]
A severe clinicopathologic phenotype of RAF1 Ser257Leu neomutation in a preterm infant without cardiac anomaly. — Darouich S, Chakroun AS, Bellamine H, Khamassi I American journal of medical genetics. Part A (2023)
[22]
Proptosis secondary to bilateral extraocular muscle enlargement in Noonan syndrome with hypertrophic cardiomyopathy: A case report. — Marchione G, Pilotto E, Midena G European journal of ophthalmology (2023)
[23]
Noonan syndrome: Neuroimaging findings and morphometric analysis of the cranium base and posterior fossa in children. — Ayaz E, Yıldırım R, Çelebi C, Ozalkak S Journal of neuroimaging : official journal of the American Society of Neuroimaging (2023)
[24]
The added value of the electrocardiogram in Noonan syndrome. — Vos E, Leenders E, Werkman SR, Udink Ten Cate FEA, Draaisma JMT Cardiology in the young (2022)
[25]
A Narrative Review of the Ocular Manifestations in Noonan Syndrome. — Christou EE, Zafeiropoulos P, Rallis D, Baltogianni M, Asproudis C, Stefaniotou M et al. Seminars in ophthalmology (2022)
[26]
Male infant with Noonan syndrome with — Hagino M, Ota C, Onoki T, Iwasawa S BMJ case reports (2022)
[27]
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The clinical significance of A2ML1 variants in Noonan syndrome has to be reconsidered. — Brinkmann J, Lissewski C, Pinna V, Vial Y, Pantaleoni F, Lepri F et al. European journal of human genetics : EJHG (2021)
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Noonan syndrome patients beyond the obvious phenotype: A potential unfavorable metabolic profile. — Noronha RM, Villares SMF, Torres N, Quedas EPS, Homma TK, Albuquerque EVA et al. American journal of medical genetics. Part A (2021)
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Noonan syndrome-associated biallelic LZTR1 mutations cause cardiac hypertrophy and vascular malformations in zebrafish. — Nakagama Y, Takeda N, Ogawa S, Takeda H, Furutani Y, Nakanishi T et al. Molecular genetics & genomic medicine (2020)
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Oskar Kobyliński (1856-1926) and the first description of Noonan syndrome in the medical literature. — Marcinowski F Journal of medical biography (2020)
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Investigating the reason for loss-of-function of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) caused by Y279C mutation through molecular dynamics simulation. — Liu WS, Wang RR, Li WY, Rong M, Liu CL, Ma Y et al. Journal of biomolecular structure & dynamics (2020)
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Providing more evidence on LZTR1 variants in Noonan syndrome patients. — Chinton J, Huckstadt V, Mucciolo M, Lepri F, Novelli A, Gravina LP et al. American journal of medical genetics. Part A (2020)
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Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p.Q510P mutation in the PTPN11 gene. — Li R, Baskfield A, Lin Y, Beers J, Zou J, Liu C et al. Stem cell research (2019)
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Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions. — Leach NT, Wilson Mathews DR, Rosenblum LS, Zhou Z, Zhu H, Heim RA Genetics in medicine : official journal of the American College of Medical Genetics (2019)
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miR-195 inhibited abnormal activation of osteoblast differentiation in MC3T3-E1 cells via targeting RAF-1. — Chao C, Li F, Tan Z, Zhang W, Yang Y, Luo C Experimental cell research (2018)
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Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing. — Tafazoli A, Eshraghi P, Pantaleoni F, Vakili R, Moghaddassian M, Ghahraman M et al. Advances in medical sciences (2018)
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Preoperative Detailed Coagulation Tests Are Required in Patients With Noonan Syndrome. — Morice A, Harroche A, Cairet P, Khonsari RH Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons (2018)
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The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor. — Harms FL, Alawi M, Amor DJ, Tan TY, Cuturilo G, Lissewski C et al. American journal of medical genetics. Part A (2018)
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Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome. — Meyers AB, Awomolo AO, Szabo S Pediatric radiology (2017)
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Separate origins of the left internal and external carotid arteries from the aortic arch and cervical internal carotid artery aneurysm in a patient with Noonan syndrome. — Tahir RA, Asmaro K, Pabaney A, Kole M, Nypaver T, Marin H Journal of neurointerventional surgery (2017)
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Growth references for Japanese individuals with Noonan syndrome. — Isojima T, Sakazume S, Hasegawa T, Ogata T, Nakanishi T, Nagai T et al. Pediatric research (2016)
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Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. — Conboy E, Dhamija R, Wang M, Xie J, Dyck PJ, Bridges AG et al. Journal of medical genetics (2016)
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Coronary artery ectasia in Noonan syndrome: Report of an individual with SOS1 mutation and literature review. — Calcagni G, Baban A, De Luca E, Leonardi B, Pongiglione G, Digilio MC American journal of medical genetics. Part A (2016)
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Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype. — Koenighofer M, Hung CY, McCauley JL, Dallman J, Back EJ, Mihalek I et al. Clinical genetics (2016)
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Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations. — Yaoita M, Niihori T, Mizuno S, Okamoto N, Hayashi S, Watanabe A et al. Human genetics (2016)
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A novel heterozygous RIT1 mutation in a patient with Noonan syndrome, leukopenia, and transient myeloproliferation-a review of the literature. — Nemcikova M, Vejvalkova S, Fencl F, Sukova M, Krepelova A European journal of pediatrics (2016)
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Development of bilateral coronary artery aneurysms in a child with Noonan syndrome. — Mauro DM, Flors L, Hoyer AW, Norton PT, Hagspiel KD Pediatric radiology (2016)
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The efficacy and safety of growth hormone therapy in children with noonan syndrome: a review of the evidence. — Noonan JA, Kappelgaard AM Hormone research in paediatrics (2015)
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Attention skills and executive functioning in children with Noonan syndrome and their unaffected siblings. — Pierpont EI, Tworog-Dube E, Roberts AE Developmental medicine and child neurology (2015)
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Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome. — Vissers LE, Bonetti M, Paardekooper Overman J, Nillesen WM, Frints SG, de Ligt J et al. European journal of human genetics : EJHG (2015)
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Vascular endothelial growth factor (VEGF) levels in short, GH treated children: a distinct pattern of VEGF-C in Noonan syndrome. — Fuchs S, Gat-Yablonski G, Shtaif B, Lazar L, Phillip M, Lebenthal Y Journal of endocrinological investigation (2015)
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Expanding the clinical spectrum of ocular anomalies in Noonan syndrome: Axenfeld-anomaly in a child with PTPN11 mutation. — Guerin A, So J, Mireskandari K, Jougeh-Doust S, Chisholm C, Klatt R et al. American journal of medical genetics. Part A (2015)
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A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. — Nishi E, Mizuno S, Nanjo Y, Niihori T, Fukushima Y, Matsubara Y et al. American journal of medical genetics. Part A (2015)
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Cardiac findings in Noonan syndrome on long-term follow-up. — Colquitt JL, Noonan JA Congenital heart disease (2014)
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Frequency of aortic dilation in Noonan syndrome. — Cornwall JW, Green RS, Nielsen JC, Gelb BD The American journal of cardiology (2014)
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Pulmonary interstitial glycogenosis in a patient ultimately diagnosed with Noonan syndrome. — Ross MK, Ellis LS, Bird LM, Hagood JS Pediatric pulmonology (2014)
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Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation. — Zarate YA, Lichty AW, Champion KJ, Clarkson LK, Holden KR, Matheus MG Journal of child neurology (2014)
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Cervical characteristics of Noonan syndrome. — Miyamoto JJ, Yabunaka T, Moriyama K European journal of orthodontics (2014)
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Association between Noonan syndrome and Chiari I malformation: a case-based update. — Keh YS, Abernethy L, Pettorini B Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery (2013)
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Mutational analysis of the PTPN11 gene in Egyptian patients with Noonan syndrome. — Essawi ML, Ismail MF, Afifi HH, Kobesiy MM, El Kotoury A, Barakat MM Journal of the Formosan Medical Association = Taiwan yi zhi (2013)
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Conservative management of severe open bite and feeding difficulties in patient with noonan syndrome. — Fonteles CS, de Miranda Mota AC, Lima RA, Borges PC, da Silveira A The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association (2013)
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Ocular manifestations of Noonan syndrome. — Marin Lda R, da Silva FT, de Sá LC, Brasil AS, Pereira A, Furquim IM et al. Ophthalmic genetics (2012)
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Bleeding disorders in Noonan syndrome. — Briggs BJ, Dickerman JD Pediatric blood & cancer (2012)
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Affective functioning and social cognition in Noonan syndrome. — Wingbermühle E, Egger JI, Verhoeven WM, van der Burgt I, Kessels RP Psychological medicine (2012)
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The novel concurrence of Noonan syndrome and bilateral Duane-like synkinesis. — Kerr NM, Vincent AL Journal of pediatric ophthalmology and strabismus (2011)
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Sudden death in a patient with Noonan syndrome. — Aydin A, Yilmazer MS, Gurol T Cardiology in the young (2011)
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A suggested role for mitochondria in Noonan syndrome. — Lee I, Pecinova A, Pecina P, Neel BG, Araki T, Kucherlapati R et al. Biochimica et biophysica acta (2010)
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PTPN11 mutation associated with aortic dilation and hypertrophic cardiomyopathy in a pediatric patient with Noonan syndrome. — Jefferies JL, Belmont JW, Pignatelli R, Towbin JA, Craigen WJ Pediatric cardiology (2010)
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A restricted spectrum of NRAS mutations causes Noonan syndrome. — Cirstea IC, Kutsche K, Dvorsky R, Gremer L, Carta C, Horn D et al. Nature genetics (2010)
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Mitochondrial DNA haplogroup 'R' is associated with Noonan syndrome of south India. — Rani DS, Dhandapany PS, Nallari P, Govindaraj P, Singh L, Thangaraj K Mitochondrion (2010)
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Coinheritance of Noonan syndrome and Becker muscular dystrophy. — Dinopoulos A, Papadopoulou A, Manta P, Kekou K, Kanelopoulos T, Fretzayas A et al. Neuromuscular disorders : NMD (2010)
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A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins. — Nyström AM, Ekvall S, Strömberg B, Holmström G, Thuresson AC, Annerén G et al. Acta paediatrica (Oslo, Norway : 1992) (2009)
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Response to growth hormone in short children with Noonan syndrome: correlation to genotype. — Binder G Hormone research (2009)
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Noonan syndrome: the hypothalamo-adrenal and hypothalamo-gonadal axes. — Kelnar CJ Hormone research (2009)
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Molecular characterization of a balanced rearrangement of chromosome 12 in two siblings with Noonan syndrome. — Yatsenko SA, del Valle Torrado M, Fernandes PH, Wiszniewska J, Gallego M, Herrera J et al. American journal of medical genetics. Part A (2009)
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Genetic and pathogenetic aspects of Noonan syndrome and related disorders. — Zenker M Hormone research (2009)
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Noonan syndrome caused by germline KRAS mutation in Taiwan: report of two patients and a review of the literature. — Lo FS, Lin JL, Kuo MT, Chiu PC, Shu SG, Chao MC et al. European journal of pediatrics (2009)
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Growth hormone and the heart in Noonan syndrome. — Noordam C Hormone research (2009)
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GH therapy in Noonan syndrome: Review of final height data. — Dahlgren J Hormone research (2009)
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Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome. — Neumann TE, Allanson J, Kavamura I, Kerr B, Neri G, Noonan J et al. European journal of human genetics : EJHG (2009)
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Genotype differences in cognitive functioning in Noonan syndrome. — Pierpont EI, Pierpont ME, Mendelsohn NJ, Roberts AE, Tworog-Dube E, Seidenberg MS Genes, brain, and behavior (2009)
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Noonan syndrome/leukemia-associated gain-of-function mutations in SHP-2 phosphatase (PTPN11) enhance cell migration and angiogenesis. — Wang S, Yu WM, Zhang W, McCrae KR, Neel BG, Qu CK The Journal of biological chemistry (2009)
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PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings. — Lee KA, Williams B, Roza K, Ferguson H, David K, Eddleman K et al. Clinical genetics (2009)
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Growth hormone therapy in Noonan syndrome: growth response and characteristics. — Westphal O Hormone research (2009)
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Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1. — Nyström AM, Ekvall S, Allanson J, Edeby C, Elinder M, Holmström G et al. Clinical genetics (2009)
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Growth in Noonan syndrome. — Otten BJ, Noordam C Hormone research (2009)
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Noonan syndrome: growth to growth hormone - the experience of observational studies. — Ranke MB Hormone research (2009)
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Neuropsychological and behavioral aspects of Noonan syndrome. — Wingbermuehle E, Egger J, van der Burgt I, Verhoeven W Hormone research (2009)
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Perinatal autopsy findings in three cases of jugular lymphatic obstruction sequence and cardiac polyvalvular dysplasia. — Bendon R, Asamoah A Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society (2008)
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Tumor development in three patients with Noonan syndrome. — Fryssira H, Leventopoulos G, Psoni S, Kitsiou-Tzeli S, Stavrianeas N, Kanavakis E European journal of pediatrics (2008)
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Visual function in Noonan and LEOPARD syndrome. — Alfieri P, Cesarini L, Zampino G, Pantaleoni F, Selicorni A, Salerni A et al. Neuropediatrics (2008)
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Mild variable Noonan syndrome in a family with a novel PTPN11 mutation. — Zenker M, Voss E, Reis A European journal of medical genetics (2007)
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Novel mitochondrial DNA mutations implicated in Noonan syndrome. — Dhandapany PS, Sadayappan S, Vanniarajan A, Karthikeyan B, Nagaraj C, Gowrishankar K et al. International journal of cardiology (2007)
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