{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:55:21Z","timestamp":1790999721958,"version":"4.1.0"},"reference-count":135,"publisher":"Japanese Society for Pediatric Endocrinology","issue":"4","funder":[{"name":"Ministry of Health, Labour and Welfare\/Research on rare and intractable diseases Program","award":["23FC1040"],"award-info":[{"award-number":["23FC1040"]}],"id":[{"id":"https:\/\/ror.org\/03mwa7s65","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23ek0109618"],"award-info":[{"award-number":["JP23ek0109618"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pediatr Endocrinol"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1297\/cpe.2026-0037","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:09:29Z","timestamp":1779314969000},"page":"319-336","source":"Crossref","is-referenced-by-count":0,"title":["Clinical consensus guidelines for the management of Noonan syndrome in Japan"],"prefix":"10.1297","volume":"35","author":[{"given":"Masanobu","family":"Kawai","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Endocrinology, Research Institute, Osaka Women\u2019s and Children\u2019s Hospital, Izumi, Japan"},{"name":"Department of Gastroenterology, Nutrition, and Endocrinology, Osaka Women\u2019s and Children\u2019s Hospital, Izumi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Osaka Graduate School of Medicine, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Osaka Graduate School of Medicine, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Muroya","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Kanagawa Children\u2019s Medical Center, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Children Medical Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kurosawa","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hamamatsu Medical Center, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"125","reference":[{"key":"1","unstructured":"1. Noonan, JA, Ehmke, DA. Associated noncardiac malformations in children with congenital heart disease. Midwest Soc Pediatr Res. 1963;63: 468\u201370."},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Noonan, JA. Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease. Am J Dis Child 1968;116: 373\u201380.","DOI":"10.1001\/archpedi.1968.02100020377005"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Yamamoto, GL, Aguena, M, Gos, M, Hung, C, Pilch, J, Fahiminiya, S, et al. Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. J Med Genet 2015;52: 413\u201321.","DOI":"10.1136\/jmedgenet-2015-103018"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. 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: 425\u201339.","DOI":"10.1002\/ajmg.c.32012"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. van der Burgt, I, Berends, E, Lommen, E, van Beersum, S, Hamel, B, Mariman, E. Clinical and molecular studies in a large Dutch family with Noonan syndrome. Am J Med Genet 1994;53: 187\u201391.","DOI":"10.1002\/ajmg.1320530213"},{"key":"6","doi-asserted-by":"publisher","unstructured":"6. Roberts, AE, Allanson, JE, Tartaglia, M, Gelb, BD. Noonan syndrome. Lancet 2013;381: 333\u201342.","DOI":"10.1016\/S0140-6736(12)61023-X"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Aoki, Y, Niihori, T, Inoue, S, Matsubara, Y. Recent advances in RASopathies. J Hum Genet 2016;61: 33\u20139.","DOI":"10.1038\/jhg.2015.114"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Tartaglia, M, Mehler, EL, Goldberg, R, Zampino, G, Brunner, HG, Kremer, H, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 2001;29: 465\u20138.","DOI":"10.1038\/ng772"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Roberts, AE, Araki, T, Swanson, KD, Montgomery, KT, Schiripo, TA, Joshi, VA, et al. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet 2007;39: 70\u20134.","DOI":"10.1038\/ng1926"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Tartaglia, M, Pennacchio, LA, Zhao, C, Yadav, KK, Fodale, V, Sarkozy, A, et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet 2007;39: 75\u20139.","DOI":"10.1038\/ng1939"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Pandit, B, Sarkozy, A, Pennacchio, LA, Carta, C, Oishi, K, Martinelli, S, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet 2007;39: 1007\u201312.","DOI":"10.1038\/ng2073"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Razzaque, MA, Nishizawa, T, Komoike, Y, Yagi, H, Furutani, M, Amo, R, et al. Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet 2007;39: 1013\u20137.","DOI":"10.1038\/ng2078"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Schubbert, S, Zenker, M, Rowe, SL, B\u00f6ll, S, Klein, C, Bollag, G, et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet 2006;38: 331\u20136.","DOI":"10.1038\/ng1748"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Cirstea, IC, Kutsche, K, Dvorsky, R, Gremer, L, Carta, C, Horn, D, et al. A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet 2010;42: 27\u20139.","DOI":"10.1038\/ng.497"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Aoki, Y, Niihori, T, Banjo, T, Okamoto, N, Mizuno, S, Kurosawa, K, et al. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS\/MAPK pathway syndrome. Am J Hum Genet 2013;93: 173\u201380.","DOI":"10.1016\/j.ajhg.2013.05.021"},{"key":"16","unstructured":"16. Roberts, AE. Noonan Syndrome. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, eds. GeneReviews((R)). Seattle (WA) 1993."},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Prendiville, TW, Gauvreau, K, Tworog-Dube, E, Patkin, L, Kucherlapati, RS, Roberts, AE, et al. Cardiovascular disease in Noonan syndrome. Arch Dis Child 2014;99: 629\u201334.","DOI":"10.1136\/archdischild-2013-305047"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Guyatt, GH, Oxman, AD, Vist, GE, Kunz, R, Falck-Ytter, Y, Alonso-Coello, P, et al. GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336: 924\u20136.","DOI":"10.1136\/bmj.39489.470347.AD"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Grant, AR, Cushman, BJ, Cav\u00e9, H, Dillon, MW, Gelb, BD, Gripp, KW, et al. Assessing the gene-disease association of 19 genes with the RASopathies using the ClinGen gene curation framework. Hum Mutat 2018;39: 1485\u201393.","DOI":"10.1002\/humu.23624"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Flex, E, Jaiswal, M, Pantaleoni, F, Martinelli, S, Strullu, M, Fansa, EK, et al. Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis. Hum Mol Genet 2014;23: 4315\u201327.","DOI":"10.1093\/hmg\/ddu148"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Niihori, T, Nagai, K, Fujita, A, Ohashi, H, Okamoto, N, Okada, S, et al. Germline-activating RRAS2 mutations cause noonan syndrome. Am J Hum Genet 2019;104: 1233\u201340.","DOI":"10.1016\/j.ajhg.2019.04.014"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Capri, Y, Flex, E, Krumbach, OHF, Carpentieri, G, Cecchetti, S, Li\u00dfewski, C, et al. Activating mutations of RRAS2 are a rare cause of Noonan syndrome. Am J Hum Genet 2019;104: 1223\u201332.","DOI":"10.1016\/j.ajhg.2019.04.013"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Popov, IK, Hiatt, SM, Whalen, S, Keren, B, Ruivenkamp, C, van Haeringen, A, et al. A YWHAZ variant associated with cardiofaciocutaneous syndrome activates the RAF-ERK pathway. Front Physiol 2019;10: 388.","DOI":"10.3389\/fphys.2019.00388"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Motta, M, Pannone, L, Pantaleoni, F, Bocchinfuso, G, Radio, FC, Cecchetti, S, et al. Enhanced MAPK1 function causes a neurodevelopmental disorder within the RASopathy clinical spectrum. Am J Hum Genet 2020;107: 499\u2013513.","DOI":"10.1016\/j.ajhg.2020.06.018"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Motta, M, Fasano, G, Gredy, S, Brinkmann, J, Bonnard, AA, Simsek-Kiper, PO, et al. SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype. Am J Hum Genet 2021;108: 2112\u201329.","DOI":"10.1016\/j.ajhg.2021.09.007"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Yamada, M, Funato, M, Kondo, G, Suzuki, H, Uehara, T, Takenouchi, T, et al. Noonan syndrome-like phenotype in a patient with heterozygous ERF truncating variant. Congenit Anom (Kyoto) 2021;61: 226\u201330.","DOI":"10.1111\/cga.12435"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Dentici, ML, Niceta, M, Lepri, FR, Mancini, C, Priolo, M, Bonnard, AA, et al. Loss-of-function variants in ERF are associated with a Noonan syndrome-like phenotype with or without craniosynostosis. Eur J Hum Genet 2024;32: 954\u201363.","DOI":"10.1038\/s41431-024-01642-7"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Hirano, Y, Kuroda, Y, Enomoto, Y, Naruto, T, Muroya, K, Kurosawa, K. Noonan syndrome-like phenotype associated with an ERF frameshift variant. Am J Med Genet A 2024;194: e63652.","DOI":"10.1002\/ajmg.a.63652"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Goto, Y, Niihori, T, Mizuno, S, Okamoto, N, Ogata, T, Kurosawa, K, et al. Missense and truncated variants in ERF in individuals with a Noonan-like phenotype without craniosynostosis. Sci Rep 2025;15: 15179.","DOI":"10.1038\/s41598-025-89719-1"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. 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. Eur J Hum Genet 2021;29: 524\u20137.","DOI":"10.1038\/s41431-020-00743-3"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Niihori, T, Aoki, Y, Narumi, Y, Neri, G, Cav\u00e9, H, Verloes, A, et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet 2006;38: 294\u20136.","DOI":"10.1038\/ng1749"},{"key":"32","doi-asserted-by":"publisher","unstructured":"32. Rodriguez-Viciana, P, Tetsu, O, Tidyman, WE, Estep, AL, Conger, BA, Cruz, MS, et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science 2006;311: 1287\u201390.","DOI":"10.1126\/science.1124642"},{"key":"33","unstructured":"33. Rauen, KA. Cardiofaciocutaneous Syndrome. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews((R)). Seattle (WA) 1993."},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. van der Burgt, I. Noonan syndrome. Orphanet J Rare Dis 2007;2: 4.","DOI":"10.1186\/1750-1172-2-4"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Allanson, JE, Hall, JG, Hughes, HE, Preus, M, Witt, RD. Noonan syndrome: the changing phenotype. Am J Med Genet 1985;21: 507\u201314.","DOI":"10.1002\/ajmg.1320210313"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Horikawa, R, Ogata, T, Matsubara, Y, Yokoya, S, Ogawa, Y, Nishijima, K, et al. Long-term efficacy and safety of two doses of Norditropin<sup>\u00ae<\/sup> (somatropin) in Noonan syndrome: a 4-year randomized, double-blind, multicenter trial in Japanese patients. Endocr J 2020;67: 803\u201318.","DOI":"10.1507\/endocrj.EJ19-0371"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Ranke, MB, Heidemann, P, Knupfer, C, Enders, H, Schmaltz, AA, Bierich, JR. Noonan syndrome: growth and clinical manifestations in 144 cases. Eur J Pediatr 1988;148: 220\u20137.","DOI":"10.1007\/BF00441408"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Isojima, T, Kato, N, Ito, Y, Kanzaki, S, Murata, M. Growth standard charts for Japanese children with mean and standard deviation (SD) values based on the year 2000 national survey. Clin Pediatr Endocrinol 2016;25: 71\u20136.","DOI":"10.1297\/cpe.25.71"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Pierpont, ME, Digilio, MC. Cardiovascular disease in Noonan syndrome. Curr Opin Pediatr 2018;30: 601\u20138.","DOI":"10.1097\/MOP.0000000000000669"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Ly, R, Soulat, G, Iserin, L, Ladouceur, M. Coronary artery disease in adults with Noonan syndrome: Case series and literature review. Arch Cardiovasc Dis 2021;114: 598\u2013605.","DOI":"10.1016\/j.acvd.2021.06.006"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41. Cornwall, JW, Green, RS, Nielsen, JC, Gelb, BD. Frequency of aortic dilation in Noonan syndrome. Am J Cardiol 2014;113: 368\u201371.","DOI":"10.1016\/j.amjcard.2013.09.034"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. Delogu, AB, Limongelli, G, Versacci, P, Adorisio, R, Kaski, JP, Blandino, R, et al. The heart in RASopathies. Am J Med Genet C Semin Med Genet 2022;190: 440\u201351.","DOI":"10.1002\/ajmg.c.32014"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. Lee, DA, Portnoy, S, Hill, P, Gillberg, C, Patton, MA. Psychological profile of children with Noonan syndrome. Dev Med Child Neurol 2005;47: 35\u20138.","DOI":"10.1111\/j.1469-8749.2005.tb01037.x"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Perrino, F, Licchelli, S, Serra, G, Piccini, G, Caciolo, C, Pasqualetti, P, et al. Psychopathological features in Noonan syndrome. Eur J Paediatr Neurol 2018;22: 170\u20137.","DOI":"10.1016\/j.ejpn.2017.09.009"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45. Wingberm\u00fchle, E, Roelofs, RL, van der Burgt, I, Souren, PM, Verhoeven, WM, Kessels, RP, et al. Cognitive functioning of adults with Noonan syndrome: a case-control study. Genes Brain Behav 2012;11: 785\u201393.","DOI":"10.1111\/j.1601-183X.2012.00821.x"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46. Isojima, T, Sakazume, S, Hasegawa, T, Ogata, T, Nakanishi, T, Nagai, T, et al. Growth references for Japanese individuals with Noonan syndrome. Pediatr Res 2016;79: 543\u20138.","DOI":"10.1038\/pr.2015.254"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47. 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. Hum Genet 2016;135: 209\u201322.","DOI":"10.1007\/s00439-015-1627-5"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48. Shoji, Y, Hata, A, Maeyama, T, Wada, T, Hasegawa, Y, Nishi, E, et al. Genetic backgrounds and genotype-phenotype relationships in anthropometric parameters of 116 Japanese individuals with Noonan syndrome. Clin Pediatr Endocrinol 2024;33: 50\u20138.","DOI":"10.1297\/cpe.2024-0005"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49. Zenker, M, Buheitel, G, Rauch, R, Koenig, R, Bosse, K, Kress, W, et al. Genotype-phenotype correlations in Noonan syndrome. J Pediatr 2004;144: 368\u201374.","DOI":"10.1016\/j.jpeds.2003.11.032"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50. Patti, G, Scaglione, M, Maiorano, NG, Rosti, G, Divizia, MT, Camia, T, et al. Abnormalities of pubertal development and gonadal function in Noonan syndrome. Front Endocrinol (Lausanne) 2023;14: 1213098.","DOI":"10.3389\/fendo.2023.1213098"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51. Rezende, RC, Noronha, RM, Keselman, A, Quedas, EPS, Dantas, NCB, Andrade, NLM, et al. Delayed puberty phenotype observed in noonan syndrome is more pronounced in girls than boys. Horm Res Paediatr 2022;95: 51\u201361.","DOI":"10.1159\/000522670"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52. Moniez, S, Pienkowski, C, Lepage, B, Hamdi, S, Daudin, M, Oliver, I, et al. Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency. Eur J Endocrinol 2018;179: 409\u201318.","DOI":"10.1530\/EJE-18-0582"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53. da Silva, FM, Jorge, AA, Malaquias, A, da Costa Pereira, A, Yamamoto, GL, Kim, CA, et al. Nutritional aspects of Noonan syndrome and Noonan-related disorders. Am J Med Genet A 2016;170: 1525\u201331.","DOI":"10.1002\/ajmg.a.37639"},{"key":"54","doi-asserted-by":"crossref","unstructured":"54. Tamburrino, F, Mazzanti, L, Scarano, E, Gibertoni, D, Sirolli, M, Zioutas, M, et al. Lipid profile in Noonan syndrome and related disorders: trend by age, sex and genotype. Front Endocrinol (Lausanne) 2023;14: 1209339.","DOI":"10.3389\/fendo.2023.1209339"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55. Sharland, M, Burch, M, McKenna, WM, Paton, MA. A clinical study of Noonan syndrome. Arch Dis Child 1992;67: 178\u201383.","DOI":"10.1136\/adc.67.2.178"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56. Svensson, J, Carlsson, A, Ericsson, UB, Westphal, O, Ivarsson, SA. Noonan\u2019s syndrome and autoimmune diseases. J Pediatr Endocrinol Metab 2003;16: 217\u20138.","DOI":"10.1515\/JPEM.2003.16.2.217"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57. Delagrange, M, Rousseau, V, Cessans, C, Pienkowski, C, Oliver, I, Jouret, B, et al. Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels. Bone 2021;153: 116170.","DOI":"10.1016\/j.bone.2021.116170"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58. Baldassarre, G, Mussa, A, Carli, D, Molinatto, C, Ferrero, GB. Constitutional bone impairment in Noonan syndrome. Am J Med Genet A 2017;173: 692\u20138.","DOI":"10.1002\/ajmg.a.38086"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59. Shaw, AC, Kalidas, K, Crosby, AH, Jeffery, S, Patton, MA. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child 2007;92: 128\u201332.","DOI":"10.1136\/adc.2006.104547"},{"key":"60","doi-asserted-by":"crossref","unstructured":"60. Chen, Q, Hong, D, Huang, Y, Zhang, Z, Wang, S. Phenotypic and genotypic spectrum of noonan syndrome: A retrospective analysis of 46 consecutive pediatric patients presented at a regional cardiac center in China. Heliyon 2024;10: e27038.","DOI":"10.1016\/j.heliyon.2024.e27038"},{"key":"61","doi-asserted-by":"crossref","unstructured":"61. Shehade-Awwad, N, Yeshayahu, Y, Pinhas-Hamiel, O, Katz, U. Differences in severity of cardiovascular anomalies in children with Noonan syndrome based on the causative gene. Front Pediatr 2022;10: 946071.","DOI":"10.3389\/fped.2022.946071"},{"key":"62","doi-asserted-by":"crossref","unstructured":"62. Sun, L, Xie, YM, Wang, SS, Zhang, ZW. Cardiovascular abnormalities and gene mutations in children with Noonan syndrome. Front Genet 2022;13: 915129.","DOI":"10.3389\/fgene.2022.915129"},{"key":"63","doi-asserted-by":"crossref","unstructured":"63. Lee, CL, Tan, LTH, Lin, HY, Hwu, WL, Lee, NC, Chien, YH, et al. Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan. Am J Med Genet A 2020;182: 357\u201364.","DOI":"10.1002\/ajmg.a.61429"},{"key":"64","doi-asserted-by":"crossref","unstructured":"64. Calcagni, G, Limongelli, G, D\u2019Ambrosio, A, Gesualdo, F, Digilio, MC, Baban, A, et al. Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results. Int J Cardiol 2017;245: 92\u20138.","DOI":"10.1016\/j.ijcard.2017.07.068"},{"key":"65","doi-asserted-by":"crossref","unstructured":"65. Colquitt, JL, Noonan, JA. Cardiac findings in Noonan syndrome on long-term follow-up. Congenit Heart Dis 2014;9: 144\u201350.","DOI":"10.1111\/chd.12102"},{"key":"66","doi-asserted-by":"crossref","unstructured":"66. Raaijmakers, R, Noordam, C, Noonan, JA, Croonen, EA, van der Burgt, CJ, Draaisma, JM. Are ECG abnormalities in Noonan syndrome characteristic for the syndrome? Eur J Pediatr 2008;167: 1363\u20137.","DOI":"10.1007\/s00431-008-0670-9"},{"key":"67","doi-asserted-by":"crossref","unstructured":"67. Levin, MD, Saitta, SC, Gripp, KW, Wenger, TL, Ganesh, J, Kalish, JM, et al. Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients. Am J Med Genet A 2018;176: 1711\u201322.","DOI":"10.1002\/ajmg.a.38854"},{"key":"68","doi-asserted-by":"crossref","unstructured":"68. Boleti, O, Norrish, G, Field, E, Dady, K, Summers, K, Nepali, G, et al. Natural history and outcomes in paediatric RASopathy-associated hypertrophic cardiomyopathy. ESC Heart Fail 2024;11: 923\u201336.","DOI":"10.1002\/ehf2.14637"},{"key":"69","doi-asserted-by":"crossref","unstructured":"69. Lynch, A, Tatangelo, M, Ahuja, S, Steve Fan, CP, Min, S, Lafreniere-Roula, M, et al. Risk of sudden death in patients with RASopathy hypertrophic cardiomyopathy. J Am Coll Cardiol 2023;81: 1035\u201345.","DOI":"10.1016\/j.jacc.2023.01.012"},{"key":"70","doi-asserted-by":"crossref","unstructured":"70. Boleti, OD, Roussos, S, Norrish, G, Field, E, Oates, S, Tollit, J, et al. Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: Validation of the HCM risk-kids model and predictors of events. Int J Cardiol 2023;393: 131405.","DOI":"10.1016\/j.ijcard.2023.131405"},{"key":"71","doi-asserted-by":"crossref","unstructured":"71. van Trier, DC, van der Burgt, I, Draaijer, RW, Cruysberg, JRM, Noordam, C, Draaisma, JM. Ocular findings in Noonan syndrome: a retrospective cohort study of 105 patients. Eur J Pediatr 2018;177: 1293\u20138.","DOI":"10.1007\/s00431-018-3183-1"},{"key":"72","doi-asserted-by":"crossref","unstructured":"72. Madej, O, Kiff, R, Kubba, H. How common are ear, nose and throat disorders in children with Noonan syndrome and other RASopathies? Int J Pediatr Otorhinolaryngol 2023;166: 111480.","DOI":"10.1016\/j.ijporl.2023.111480"},{"key":"73","doi-asserted-by":"crossref","unstructured":"73. van Trier, DC, van Nierop, J, Draaisma, JMT, van der Burgt, I, Kunst, H, Croonen, EA, et al. External ear anomalies and hearing impairment in Noonan Syndrome. Int J Pediatr Otorhinolaryngol 2015;79: 874\u20138.","DOI":"10.1016\/j.ijporl.2015.03.021"},{"key":"74","doi-asserted-by":"crossref","unstructured":"74. Nugent, DJ, Romano, AA, Sabharwal, S, Cooper, DL. Evaluation of bleeding disorders in patients with Noonan syndrome: a systematic review. J Blood Med 2018;9: 185\u201392.","DOI":"10.2147\/JBM.S164474"},{"key":"75","doi-asserted-by":"crossref","unstructured":"75. Briggs, B, Savla, D, Ramchandar, N, Dimmock, D, Le, D, Thornburg, CD. The evaluation of hematologic screening and perioperative management in patients with noonan syndrome: a retrospective chart review. J Pediatr 2020;220: 154\u2013158.e6.","DOI":"10.1016\/j.jpeds.2020.01.048"},{"key":"76","doi-asserted-by":"crossref","unstructured":"76. Kratz, CP, Franke, L, Peters, H, Kohlschmidt, N, Kazmierczak, B, Finckh, U, et al. Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes. Br J Cancer 2015;112: 1392\u20137.","DOI":"10.1038\/bjc.2015.75"},{"key":"77","doi-asserted-by":"crossref","unstructured":"77. Jongmans, MC, van der Burgt, I, Hoogerbrugge, PM, Noordam, K, Yntema, HG, Nillesen, WM, et al. Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. Eur J Hum Genet 2011;19: 870\u20134.","DOI":"10.1038\/ejhg.2011.37"},{"key":"78","doi-asserted-by":"crossref","unstructured":"78. Piotrowski, A, Xie, J, Liu, YF, Poplawski, AB, Gomes, AR, Madanecki, P, et al. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas. Nat Genet 2014;46: 182\u20137.","DOI":"10.1038\/ng.2855"},{"key":"79","doi-asserted-by":"crossref","unstructured":"79. Villani, A, Greer, MC, Kalish, JM, Nakagawara, A, Nathanson, KL, Pajtler, KW, et al. Recommendations for cancer surveillance in individuals with RASopathies and other rare genetic conditions with increased cancer risk. Clin Cancer Res 2017;23: e83\u201390.","DOI":"10.1158\/1078-0432.CCR-17-0631"},{"key":"80","doi-asserted-by":"crossref","unstructured":"80. Ueda, K, Yaoita, M, Niihori, T, Aoki, Y, Okamoto, N. Craniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype. Am J Med Genet A 2017;173: 2346\u201352.","DOI":"10.1002\/ajmg.a.38337"},{"key":"81","doi-asserted-by":"crossref","unstructured":"81. Barbero, AIS, Valenzuela, I, Fern\u00e1ndez-Alvarez, P, Vazquez, \u00c9, Cueto-Gonzalez, AM, Lasa-Aranzasti, A, et al. New insights into the spectrum of RASopathies: clinical and genetic data in a cohort of 121 Spanish patients. Am J Med Genet A 2025;197: e63905.","DOI":"10.1002\/ajmg.a.63905"},{"key":"82","doi-asserted-by":"crossref","unstructured":"82. Twigg, SR, Vorgia, E, McGowan, SJ, Peraki, I, Fenwick, AL, Sharma, VP, et al. Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1\/2 signaling to regulation of osteogenesis. Nat Genet 2013;45: 308\u201313.","DOI":"10.1038\/ng.2539"},{"key":"83","doi-asserted-by":"crossref","unstructured":"83. Glass, GE, O\u2019Hara, J, Canham, N, Cilliers, D, Dunaway, D, Fenwick, AL, et al. ERF-related craniosynostosis: The phenotypic and developmental profile of a new craniosynostosis syndrome. Am J Med Genet A 2019;179: 615\u201327.","DOI":"10.1002\/ajmg.a.61073"},{"key":"84","doi-asserted-by":"publisher","unstructured":"84. Romano, AA, Allanson, JE, Dahlgren, J, Gelb, BD, Hall, B, Pierpont, ME, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics 2010;126: 746\u201359.","DOI":"10.1542\/peds.2009-3207"},{"key":"85","doi-asserted-by":"crossref","unstructured":"85. Pierpont, EI. Neuropsychological functioning in individuals with noonan syndrome: a systematic literature review with educational and treatment recommendations. Pediatr Neuropsychol. 2016;2: 14\u201333.","DOI":"10.1007\/s40817-015-0005-5"},{"key":"86","doi-asserted-by":"crossref","unstructured":"86. Stagi, S, Ferrari, V, Ferrari, M, Priolo, M, Tartaglia, M. Inside the Noonan \u201cuniverse\u201d: Literature review on growth, GH\/IGF axis and rhGH treatment: Facts and concerns. Front Endocrinol (Lausanne) 2022;13: 951331.","DOI":"10.3389\/fendo.2022.951331"},{"key":"87","doi-asserted-by":"crossref","unstructured":"87. Sodero, G, Cipolla, C, Pane, LC, Sessa, L, Malavolta, E, Arzilli, F, et al. Efficacy and safety of growth hormone therapy in children with Noonan syndrome. Growth Horm IGF Res 2023;69-70: 101532.","DOI":"10.1016\/j.ghir.2023.101532"},{"key":"88","doi-asserted-by":"crossref","unstructured":"88. Romano, AA, Dana, K, Bakker, B, Davis, DA, Hunold, JJ, Jacobs, J, et al. Growth response, near-adult height, and patterns of growth and puberty in patients with noonan syndrome treated with growth hormone. J Clin Endocrinol Metab 2009;94: 2338\u201344.","DOI":"10.1210\/jc.2008-2094"},{"key":"89","doi-asserted-by":"crossref","unstructured":"89. Lucas, BJ, Connors, JS, Wang, H, Conneely, S, Cuglievan, B, Garcia, MB, et al. Observation and management of juvenile myelomonocytic leukemia and Noonan syndrome-associated myeloproliferative disorder: a real-world experience. Cancers (Basel) 2024;16: 2749.","DOI":"10.3390\/cancers16152749"},{"key":"90","doi-asserted-by":"crossref","unstructured":"90. Osio, D, Dahlgren, J, Wikland, KA, Westphal, O. Improved final height with long-term growth hormone treatment in Noonan syndrome. Acta Paediatr 2005;94: 1232\u20137.","DOI":"10.1111\/j.1651-2227.2005.tb02081.x"},{"key":"91","doi-asserted-by":"crossref","unstructured":"91. Moos, D, Droitcourt, C, Rancherevince, D, Marec Berard, P, Skowron, F. Atypical granular cell tumor occurring in an individual with Noonan syndrome treated with growth hormone. Pediatr Dermatol 2012;29: 665\u20136.","DOI":"10.1111\/j.1525-1470.2011.01641.x"},{"key":"92","doi-asserted-by":"crossref","unstructured":"92. Rohrer, TR, Abuzzahab, J, Backeljauw, P, Birkeg\u00e5rd, AC, Blair, J, Dahlgren, J, et al. Long-term effectiveness and safety of childhood growth hormone treatment in Noonan syndrome. Horm Res Paediatr 2020;93: 380\u201395.","DOI":"10.1159\/000512429"},{"key":"93","doi-asserted-by":"crossref","unstructured":"93. Cianfarani, S. Safety of pediatric rhGH therapy: an overview and the need for long-term surveillance. Front Endocrinol (Lausanne) 2021;12: 811846.","DOI":"10.3389\/fendo.2021.811846"},{"key":"94","doi-asserted-by":"crossref","unstructured":"94. Witkowski, L, Dillon, MW, Murphy, E, S Lebo, M, Mason-Suares, H. Expanding the Noonan spectrum\/RASopathy NGS panel: benefits of adding NF1 and SPRED1. Mol Genet Genomic Med 2020;8: e1180.","DOI":"10.1002\/mgg3.1180"},{"key":"95","doi-asserted-by":"crossref","unstructured":"95. Denayer, E, Devriendt, K, de Ravel, T, Van Buggenhout, G, Smeets, E, Francois, I, et al. Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations. Genes Chromosomes Cancer 2010;49: 242\u201352.","DOI":"10.1002\/gcc.20735"},{"key":"96","doi-asserted-by":"crossref","unstructured":"96. Bangalore Krishna, K, Pagan, P, Escobar, O, Popovic, J. Occurrence of cranial neoplasms in pediatric patients with Noonan syndrome receiving growth hormone: is screening with brain MRI prior to initiation of growth hormone indicated? Horm Res Paediatr 2017;88: 423\u20136.","DOI":"10.1159\/000479107"},{"key":"97","doi-asserted-by":"crossref","unstructured":"97. Jacquinet, A, Bonnard, A, Capri, Y, Martin, D, Sadzot, B, Bianchi, E, et al. Oligo-astrocytoma in LZTR1-related Noonan syndrome. Eur J Med Genet 2020;63: 103617.","DOI":"10.1016\/j.ejmg.2019.01.007"},{"key":"98","doi-asserted-by":"crossref","unstructured":"98. Kaya, Z, Keser, E, Atalay, E, Kayhan, G, Karamercan, S, Topuz, B, et al. Two distinct syndromic children with T-acute lymphoblastic leukemia: Noonan syndrome and Sotos syndrome. Leuk Res 2022;123: 106981.","DOI":"10.1016\/j.leukres.2022.106981"},{"key":"99","doi-asserted-by":"crossref","unstructured":"99. Cotterill, AM, McKenna, WJ, Brady, AF, Sharland, M, Elsawi, M, Yamada, M, et al. The short-term effects of growth hormone therapy on height velocity and cardiac ventricular wall thickness in children with Noonan\u2019s syndrome. J Clin Endocrinol Metab 1996;81: 2291\u20137.","DOI":"10.1210\/jcem.81.6.8964866"},{"key":"100","doi-asserted-by":"crossref","unstructured":"100. MacFarlane, CE, Brown, DC, Johnston, LB, Patton, MA, Dunger, DB, Savage, MO, et al. Growth hormone therapy and growth in children with Noonan\u2019s syndrome: results of 3 years\u2019 follow-up. J Clin Endocrinol Metab 2001;86: 1953\u20136.","DOI":"10.1210\/jcem.86.5.7468"},{"key":"101","doi-asserted-by":"crossref","unstructured":"101. Noordam, C, Draaisma, JM, van den Nieuwenhof, J, van der Burgt, I, Otten, BJ, Daniels, O. Effects of growth hormone treatment on left ventricular dimensions in children with Noonan\u2019s syndrome. Horm Res 2001;56: 110\u20133.","DOI":"10.1159\/000048101"},{"key":"102","doi-asserted-by":"crossref","unstructured":"102. K\u0131z\u0131lcan \u00c7etin, S, Ramo\u011flu, MG, \u015e\u0131klar, Z, \u00d6zsu, E, Aycan, Z, Tutar, HE, et al. The effect of growth hormone therapy on cardiac outcomes in Noonan syndrome: long term follow-up results. J Clin Res Pediatr Endocrinol 2022;14: 422\u201332.","DOI":"10.4274\/jcrpe.galenos.2022.2022-12-13"},{"key":"103","doi-asserted-by":"crossref","unstructured":"103. Apperley, LJ, Ramakrishnan, R, Dharmaraj, P, Das, U, Didi, M, Blair, J, et al. Effect of growth hormone therapy in patients with Noonan syndrome: a retrospective study. Int J Endocrinol Metab 2020;18: e107292.","DOI":"10.5812\/ijem.107292"},{"key":"104","doi-asserted-by":"crossref","unstructured":"104. Raaijmakers, R, Noordam, C, Karagiannis, G, Gregory, JW, Hertel, NT, Sipil\u00e4, I, et al. Response to growth hormone treatment and final height in Noonan syndrome in a large cohort of patients in the KIGS database. J Pediatr Endocrinol Metab 2008;21: 267\u201373.","DOI":"10.1515\/JPEM.2008.21.3.267"},{"key":"105","doi-asserted-by":"crossref","unstructured":"105. Romano, AA, Blethen, SL, Dana, K, Noto, RA. Growth hormone treatment in Noonan syndrome: the National Cooperative Growth Study experience. J Pediatr 1996;128: S18\u201321.","DOI":"10.1016\/S0022-3476(96)70005-7"},{"key":"106","doi-asserted-by":"crossref","unstructured":"106. 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. Endocr J 2026;73: 229\u201341.","DOI":"10.1507\/endocrj.EJ25-0116"},{"key":"107","doi-asserted-by":"crossref","unstructured":"107. Yamagishi, H. Noonan and RAAS\/MAPK syndromes in pediatric cardiology: a review. Pediatric Cardiology and Cardiac Surgery. 2024;40: 234\u201342.","DOI":"10.9794\/jspccs.40.234"},{"key":"108","doi-asserted-by":"crossref","unstructured":"108. Chen, PC, Wakimoto, H, Conner, D, Araki, T, Yuan, T, Roberts, A, et al. Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome\u2013associated Sos1 mutation. J Clin Invest 2010;120: 4353\u201365.","DOI":"10.1172\/JCI43910"},{"key":"109","doi-asserted-by":"crossref","unstructured":"109. Wu, X, Simpson, J, Hong, JH, Kim, KH, Thavarajah, NK, Backx, PH, et al. MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1(L613V) mutation. J Clin Invest 2011;121: 1009\u201325.","DOI":"10.1172\/JCI44929"},{"key":"110","doi-asserted-by":"crossref","unstructured":"110. Cuevas-Navarro, A, Wagner, M, Van, R, Swain, M, Mo, S, Columbus, J, et al. RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy. Sci Adv 2023;9: eadf4766.","DOI":"10.1126\/sciadv.adf4766"},{"key":"111","doi-asserted-by":"crossref","first-page":"e182382","DOI":"10.1172\/jci.insight.182382","volume":"9","year":"2024","unstructured":"111. Abe, T, Morisaki, K, Niihori, T, Terao, M, Takada, S, Aoki, Y. Dysregulation of RAS proteostasis by autosomal-dominant LZTR1 mutation induces Noonan syndrome-like phenotypes in mice. JCI Insight 2024;9: e182382.","journal-title":"JCI Insight","ISSN":"https:\/\/id.crossref.org\/issn\/2379-3708","issn-type":"print"},{"key":"112","doi-asserted-by":"crossref","unstructured":"112. Kiamanesh, O, Greenway, SC, Dicke, F, Ballantyne, B, Mitrovic, S, McGrath, K, et al. Treatment of RAF1-related obstructive hypertrophic cardiomyopathy by MEK inhibition using Trametinib. JACC Case Rep 2024;29: 102379.","DOI":"10.1016\/j.jaccas.2024.102379"},{"key":"113","doi-asserted-by":"crossref","unstructured":"113. Leegaard, A, Gregersen, PA, Nielsen, TO, Bjerre, JV, Handrup, MM. Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan syndrome. Eur J Med Genet 2022;65: 104630.","DOI":"10.1016\/j.ejmg.2022.104630"},{"key":"114","doi-asserted-by":"crossref","unstructured":"114. Mussa, A, Carli, D, Giorgio, E, Villar, AM, Cardaropoli, S, Carbonara, C, et al. MEK inhibition in a newborn with <i>RAF1<\/i>-associated Noonan syndrome ameliorates hypertrophic cardiomyopathy but is insufficient to revert pulmonary vascular disease. Genes (Basel) 2021;13: 6.","DOI":"10.3390\/genes13010006"},{"key":"115","doi-asserted-by":"crossref","unstructured":"115. Pascarella, A, Limongelli, G, De Falco, A, Minale, EMP, Di Nardo, G, Di Marco, GM, et al. Refractory chylothorax and ventricular hypertrophy treated with Trametinib in a patient with Noonan syndrome: 18-month follow-up. Children (Basel) 2024;11: 11.","DOI":"10.3390\/children11111342"},{"key":"116","doi-asserted-by":"crossref","unstructured":"116. Dori, Y, Smith, C, Pinto, E, Snyder, K, March, ME, Hakonarson, H, et al. Severe lymphatic disorder resolved with MEK inhibition in a patient with Noonan syndrome and SOS1 mutation. Pediatrics 2020;146: e20200167.","DOI":"10.1542\/peds.2020-0167"},{"key":"117","doi-asserted-by":"crossref","unstructured":"117. Gordon, K, Moore, M, Van Zanten, M, Pearce, J, Itkin, M, Madden, B, et al. Case report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition. Front Genet 2022;13: 1001105.","DOI":"10.3389\/fgene.2022.1001105"},{"key":"118","doi-asserted-by":"crossref","unstructured":"118. Hribernik, I, Brooks, T, Dunlop-Jones, A, Bentham, JR. Successful treatment of refractory chylothorax with MEK inhibitor trametinib in a child with Noonan syndrome: case report. Eur Heart J Case Rep 2023;7: ytad190.","DOI":"10.1093\/ehjcr\/ytad190"},{"key":"119","doi-asserted-by":"crossref","unstructured":"119. Leenders, EKSM, Kleimeier, LER, Weeke, LC, Coppens, CH, Klein, WM, Draaisma, JMT. Trametinib restores the central conducting lymphatic flow in a premature infant with Noonan syndrome. Clin Case Rep 2024;12: e9164.","DOI":"10.1002\/ccr3.9164"},{"key":"120","doi-asserted-by":"crossref","unstructured":"120. Nakano, TA, Rankin, AW, Annam, A, Kulungowski, AM, McCallen, LM, Hill, LR, et al. Trametinib for refractory chylous effusions and systemic complications in children with Noonan syndrome. J Pediatr 2022;248: 81\u201388.e1.","DOI":"10.1016\/j.jpeds.2022.05.030"},{"key":"121","doi-asserted-by":"crossref","unstructured":"121. Lioncino, M, Fusco, A, Monda, E, Colonna, D, Sibilio, M, Caiazza, M, et al. Severe lymphatic disorder and multifocal atrial tachycardia treated with trametinib in a patient with Noonan syndrome and SOS1 mutation. Genes (Basel) 2022;13: 1503.","DOI":"10.3390\/genes13091503"},{"key":"122","doi-asserted-by":"crossref","unstructured":"122. Meisner, JK, Bradley, DJ, Russell, MW. Molecular management of multifocal atrial tachycardia in Noonan\u2019s Syndrome With MEK1\/2 inhibitor Trametinib. Circ Genom Precis Med 2021;14: e003327.","DOI":"10.1161\/CIRCGEN.121.003327"},{"key":"123","doi-asserted-by":"crossref","unstructured":"123. Wolf, CM, Zenker, M, Boleti, O, Norrish, G, Russell, M, Meisner, JK, et al. Impact of MEK inhibition on childhood RASopathy-associated hypertrophic cardiomyopathy. JACC Basic Transl Sci 2025;10: 152\u201366.","DOI":"10.1016\/j.jacbts.2024.10.002"},{"key":"124","doi-asserted-by":"crossref","unstructured":"124. Chakraborty, A, Beasley, G, Martinez, H, Jesudas, R, Anton-Martin, P, Christakopoulos, G, et al. Selumetinib for Refractory Pulmonary and Gastrointestinal Bleeding in Noonan Syndrome. Pediatrics 2022;150: e2022056336.","DOI":"10.1542\/peds.2022-056336"},{"key":"125","doi-asserted-by":"crossref","unstructured":"125. Nakajima, Y, Watanabe, Y, Iwata, K, Yamada, Y, Higuchi, S, Mori, J. Efficacy of Sirolimus in treating refractory lymphatic malformation in Noonan syndrome: a case study. JCEM Case Rep 2025;3: luaf088.","DOI":"10.1210\/jcemcr\/luaf088"},{"key":"126","doi-asserted-by":"crossref","unstructured":"126. Hahn, A, Lauriol, J, Thul, J, Behnke-Hall, K, Logeswaran, T, Sch\u00e4nzer, A, et al. Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: palliative treatment with a rapamycin analog. Am J Med Genet A 2015;167: 744\u201351.","DOI":"10.1002\/ajmg.a.36982"},{"key":"127","doi-asserted-by":"crossref","unstructured":"127. Binder, G, Grathwol, S, von Loeper, K, Blumenstock, G, Kaulitz, R, Freiberg, C, et al. Health and quality of life in adults with Noonan syndrome. J Pediatr 2012;161: 501\u2013505.e1.","DOI":"10.1016\/j.jpeds.2012.02.043"},{"key":"128","doi-asserted-by":"crossref","unstructured":"128. Kraoua, L, Jaouadi, H, Allouche, M, Achour, A, Kaouther, H, Ahmed, HB, et al. Molecular autopsy and clinical family screening in a case of sudden cardiac death reveals ACTN2 mutation related to hypertrophic\/dilated cardiomyopathy and a novel LZTR1 variant associated with Noonan syndrome. Mol Genet Genomic Med 2022;10: e1954.","DOI":"10.1002\/mgg3.1954"},{"key":"129","doi-asserted-by":"crossref","unstructured":"129. Zheng, J, Peng, L, Cheng, R, Li, Z, Xie, J, Huang, E, et al. RAF1 mutation leading to hypertrophic cardiomyopathy in a Chinese family with a history of sudden cardiac death: A diagnostic insight into Noonan syndrome. Mol Genet Genomic Med 2024;12: e2290.","DOI":"10.1002\/mgg3.2290"},{"key":"130","doi-asserted-by":"crossref","unstructured":"130. Swarts, JW, Kleimeier, LER, Leenders, EKSM, Rinne, T, Klein, WM, Draaisma, JMT. Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study. Am J Med Genet A 2022;188: 3242\u201361.","DOI":"10.1002\/ajmg.a.62955"},{"key":"131","doi-asserted-by":"crossref","unstructured":"131. Smpokou, P, Tworog-Dube, E, Kucherlapati, RS, Roberts, AE. Medical complications, clinical findings, and educational outcomes in adults with Noonan syndrome. Am J Med Genet A 2012;158A: 3106\u201311.","DOI":"10.1002\/ajmg.a.35639"},{"key":"132","doi-asserted-by":"crossref","unstructured":"132. Qiu, WW, Yin, SS, Stucker, FJ. Audiologic manifestations of Noonan syndrome. Otolaryngol Head Neck Surg 1998;118: 319\u201323.","DOI":"10.1016\/S0194-59989870308-0"},{"key":"133","doi-asserted-by":"crossref","unstructured":"133. Davico, C, D\u2019Alessandro, R, Borgogno, M, Campagna, F, Torta, F, Ricci, F, et al. Epilepsy in a cohort of children with Noonan syndrome and related disorders. Eur J Pediatr 2022;181: 2919\u201326.","DOI":"10.1007\/s00431-022-04497-6"},{"key":"134","doi-asserted-by":"crossref","unstructured":"134. Roelofs, RL, Janssen, N, Wingberm\u00fchle, E, Kessels, RP, Egger, JI. Intellectual development in Noonan syndrome: a longitudinal study. Brain Behav 2016;6: e00479.","DOI":"10.1002\/brb3.479"},{"key":"135","doi-asserted-by":"crossref","unstructured":"135. Roelofs, RL, Wingberm\u00fchle, E, van der Heijden, PT, Jonkers, R, de Haan, M, Kessels, RPC, et al. Personality and psychopathology in adults with Noonan syndrome. J Clin Psychol Med Settings 2020;27: 256\u201367.","DOI":"10.1007\/s10880-019-09659-7"}],"container-title":["Clinical Pediatric Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/35\/4\/35_2026-0037\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:40:53Z","timestamp":1790998853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/35\/4\/35_2026-0037\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":135,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1297\/cpe.2026-0037","relation":{},"ISSN":["0918-5739","1347-7358"],"issn-type":[{"value":"0918-5739","type":"print"},{"value":"1347-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"2026-0037"}}