{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:42:16Z","timestamp":1776746536859,"version":"3.51.2"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy from Cluj-Napoca, Romania","award":["Doctoral Research Program PCD 771\/48."],"award-info":[{"award-number":["Doctoral Research Program PCD 771\/48."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: RASopathies represent a clinically and genetically diverse group of syndromes resulting from germline mutations in genes regulating the RAS\/mitogen-activated protein kinase (MAPK) signaling cascade. Methods: The aim of this study was to describe the clinical features and genetic variants identified in patients with genetically confirmed Noonan syndrome (NS) in a limited cohort from Romania. A total of 25 patients with positive genetic testing for NS-associated genes were included. Genetic testing was performed primarily using next-generation sequencing. Results: A total of twenty-six variants were identified in twenty-five patients, as one patient carried two pathogenic variants in the PTPN11 gene (c.188A&gt;G and c.922A&gt;G). Of these variants, twenty-four (92.31%) were classified as pathogenic and two (7.69%) as variants of uncertain significance (VUS). Pathogenic variants were found in different genes, including PTPN11, LZTR1, SOS1, and RAF1, with PTPN11 being the most frequently affected gene. Males predominated (17\/25), with a male-to-female ratio of approximately 2:1. Two patients inherited the pathogenic variant from an affected parent. Cardiovascular involvement was present in 21 patients (84%), with pulmonary valve stenosis (PVS) being the most common finding (48%), followed by hypertrophic cardiomyopathy (16%). Additional cardiac anomalies included atrial septal defect, valvular regurgitation, dysplastic valves, coarctation of the aorta, and sinotubular junction narrowing. Short stature was observed in 64% of patients, and craniofacial dysmorphism was present in 96%. Cutaneous, ectodermal, dental, ophthalmologic, and auditory manifestations were variably observed. Conclusions: Although based on a limited cohort from Romania, this study provides insights into clinical features suggestive of NS. Our findings highlight the genetic heterogeneity of NS and emphasize the importance of comprehensive genetic testing for confirming diagnosis, guiding clinical management, and supporting family counseling.<\/jats:p>","DOI":"10.3390\/diagnostics16081207","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:30:36Z","timestamp":1776443436000},"page":"1207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Diagnosis and Phenotypic Variability of Noonan Syndrome: Experience from a Romanian Multicenter Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8864-9191","authenticated-orcid":false,"given":"Florina Victoria","family":"Nazarie","sequence":"first","affiliation":[{"name":"Discipline of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6, Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7091-4295","authenticated-orcid":false,"given":"Mihaela Amelia","family":"Dobrescu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Medicine and Pharmacy of Craiova, 2, Petru Rare\u0219 St., 200349 Craiova, Romania"},{"name":"Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7649-5308","authenticated-orcid":false,"given":"Cecilia","family":"Lazea","sequence":"additional","affiliation":[{"name":"1st Pediatric Discipline, Mother and Child Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"},{"name":"1st Pediatrics Clinic, Children\u2019s Emergency Clinical Hospital, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6374-7413","authenticated-orcid":false,"given":"Ana Adriana","family":"David","sequence":"additional","affiliation":[{"name":"1st Pediatrics Clinic, Children\u2019s Emergency Clinical Hospital, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crina","family":"\u0218ufan\u0103","sequence":"additional","affiliation":[{"name":"1st Pediatrics Clinic, Children\u2019s Emergency Clinical Hospital, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4557-0333","authenticated-orcid":false,"given":"Simona","family":"Bucerzan","sequence":"additional","affiliation":[{"name":"1st Pediatric Discipline, Mother and Child Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"},{"name":"Medical Genetics Compartment, Children\u2019s Emergency Clinical Hospital, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9500-2372","authenticated-orcid":false,"given":"Simona Sorana","family":"Cainap","sequence":"additional","affiliation":[{"name":"2nd Pediatric Department, Clinical Children Hospital, 3-5, Crisan St., 400124 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Discipline, Mother and Child Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 3-5, Crisan St., 400124 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-4352","authenticated-orcid":false,"given":"Raluca","family":"Rancea","sequence":"additional","affiliation":[{"name":"Department of Cardiology, \u201cNiculae Stancioiu\u201d Heart Institute, 19-21, Motilor St., 400001 Cluj-Napoca, Romania"},{"name":"PhD Student Doctoral School, \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy, 8, Victor Babes St., 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-7605","authenticated-orcid":false,"given":"Oana","family":"St\u0103noiu-P\u00eenzariu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 3, Pasteur St., 400349 Cluj-Napoca, Romania"},{"name":"Endocrinology Clinic, Cluj County Emergency Clinical Hospital, 3, Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0679-1379","authenticated-orcid":false,"given":"Ionela Maria","family":"Pascanu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of T\u00e2rgu Mure\u0219, 46, Gheorghe Marinescu St., 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1494-5369","authenticated-orcid":false,"given":"Radu Anghel","family":"Popp","sequence":"additional","affiliation":[{"name":"Discipline of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6, Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5806-0220","authenticated-orcid":false,"given":"Laura Ancuta","family":"Pop","sequence":"additional","affiliation":[{"name":"Genomics Department, MEDFUTURE-Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 23, Gheorghe Marinescu St., 400337 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-431X","authenticated-orcid":false,"given":"C\u0103lin","family":"Laz\u0103r","sequence":"additional","affiliation":[{"name":"1st Pediatric Discipline, Mother and Child Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"},{"name":"1st Pediatrics Clinic, Children\u2019s Emergency Clinical Hospital, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4364-7181","authenticated-orcid":false,"given":"Camelia","family":"Alkhzouz","sequence":"additional","affiliation":[{"name":"1st Pediatric Discipline, Mother and Child Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"},{"name":"Medical Genetics Compartment, Children\u2019s Emergency Clinical Hospital, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8777-0689","authenticated-orcid":false,"given":"Diana","family":"Miclea","sequence":"additional","affiliation":[{"name":"1st Pediatric Discipline, Mother and Child Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"},{"name":"Medical Genetics Compartment, Children\u2019s Emergency Clinical Hospital, 68, Calea Mo\u021bilor St., 400370 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2476-9706","authenticated-orcid":false,"given":"Romana","family":"Vulturar","sequence":"additional","affiliation":[{"name":"Discipline of Cell and Molecular Biology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6, Pasteur St., 400349 Cluj-Napoca, Romania"},{"name":"Association for Innovation in Rare Inflammatory, Metabolic, Genetic Diseases INNOROG, 400497 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/jhg.2015.114","article-title":"Recent Advances in RASopathies","volume":"61","author":"Aoki","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R123","DOI":"10.1093\/hmg\/ddw191","article-title":"Pathogenetics of the RASopathies","volume":"25","author":"Tidyman","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1750-1172-2-4","article-title":"Noonan Syndrome","volume":"2","year":"2007","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1002\/ajmg.a.33518","article-title":"The Face of Noonan Syndrome: Does Phenotype Predict Genotype","volume":"152A","author":"Allanson","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2025, December 29). Noonan Syndrome. 15 November 2001 [Updated 4 December 2025], GeneReviews\u00ae [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1124\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12102","DOI":"10.1038\/s41598-025-90635-7","article-title":"Gene Signatures and Genotype-Phenotype Correlations of Sensorineural Hearing Loss in Noonan Syndrome and Related RASopathies","volume":"15","author":"Lee","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0140-6736(12)61023-X","article-title":"Noonan Syndrome","volume":"381","author":"Roberts","year":"2013","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1093\/hmg\/ddu148","article-title":"Activating Mutations in RRAS Underlie a Phenotype within the RASopathy Spectrum and Contribute to Leukaemogenesis","volume":"23","author":"Flex","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/ejhg.2014.115","article-title":"Heterozygous Germline Mutations in A2ML1 Are Associated with a Disorder Clinically Related to Noonan Syndrome","volume":"23","author":"Vissers","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nazarie, F.V., Miclea, D., \u0218ufan\u0103, C., Botezatu, A., Popp, R.A., Pascanu, I.M., Alkhzouz, C., Bucerzan, S., Laz\u0103r, C., and Lazea, C. (2025). Clinical and Genetic Characterization of Noonan Syndrome in a Romanian Cohort from Transylvania: Details on PTPN11 c.922A>G Variant and Phenotypic Spectrum. Diagnostics, 15.","DOI":"10.3390\/diagnostics15212753"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1086\/340847","article-title":"PTPN11 Mutations in Noonan Syndrome: Molecular Spectrum, Genotype-Phenotype Correlation, and Phenotypic Heterogeneity","volume":"70","author":"Tartaglia","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/bioinformatics\/bts091","article-title":"Unipro UGENE: A Unified Bioinformatics Toolkit","volume":"28","author":"Okonechnikov","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/humu.20955","article-title":"Germline BRAF Mutations in Noonan, LEOPARD, and Cardiofaciocutaneous Syndromes: Molecular Diversity and Associated Phenotypic Spectrum","volume":"30","author":"Sarkozy","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1093\/hmg\/ddy412","article-title":"Dominant Noonan Syndrome-Causing LZTR1 Mutations Specifically Affect the Kelch Domain Substrate-Recognition Surface and Enhance RAS-MAPK Signaling","volume":"28","author":"Motta","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ng.497","article-title":"A Restricted Spectrum of NRAS Mutations Causes Noonan Syndrome","volume":"42","author":"Cirstea","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1242\/dmm.007112","article-title":"Noonan Syndrome Gain-of-Function Mutations in NRAS Cause Zebrafish Gastrulation Defects","volume":"4","author":"Runtuwene","year":"2011","journal-title":"Dis. Model. Mech."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e91225","DOI":"10.1172\/jci.insight.91225","article-title":"Elucidation of MRAS-Mediated Noonan Syndrome with Cardiac Hypertrophy","volume":"2","author":"Higgins","year":"2017","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/ng2073","article-title":"Gain-of-Function RAF1 Mutations Cause Noonan and LEOPARD Syndromes with Hypertrophic Cardiomyopathy","volume":"39","author":"Pandit","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11473","DOI":"10.1073\/pnas.1324128111","article-title":"Next-Generation Sequencing Identifies Rare Variants Associated with Noonan Syndrome","volume":"111","author":"Chen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ajhg.2013.05.021","article-title":"Gain-of-Function Mutations in RIT1 Cause Noonan Syndrome, a RAS\/MAPK Pathway Syndrome","volume":"93","author":"Aoki","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng1926","article-title":"Germline Gain-of-Function Mutations in SOS1 Cause Noonan Syndrome","volume":"39","author":"Roberts","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1136\/jmedgenet-2015-103018","article-title":"Rare Variants in SOS2 and LZTR1 Are Associated with Noonan Syndrome","volume":"52","author":"Yamamoto","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41431-020-00708-6","article-title":"Variants of SOS2 Are a Rare Cause of Noonan Syndrome with Particular Predisposition for Lymphatic Complications","volume":"29","author":"Lissewski","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/ajmg.1320530213","article-title":"Clinical and Molecular Studies in a Large Dutch Family with Noonan Syndrome","volume":"53","author":"Berends","year":"1994","journal-title":"Am. J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000243782","article-title":"Genetic and Pathogenetic Aspects of Noonan Syndrome and Related Disorders","volume":"72","author":"Zenker","year":"2009","journal-title":"Horm. Res. Paediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.molcel.2015.05.004","article-title":"High-Throughput Sequencing Technologies","volume":"58","author":"Reuter","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/pcmr.13086","article-title":"Genetic and Phenotypic Heterogeneity of Multiple Lentigines and Precise Diagnosis in Four Chinese Families with Multiple Lentigines","volume":"36","author":"Guo","year":"2023","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Athota, J.P., Bhat, M., Nampoothiri, S., Gowrishankar, K., Narayanachar, S.G., Puttamallesh, V., Farooque, M.O., and Shetty, S. (2020). Molecular and Clinical Studies in 107 Noonan Syndrome Affected Individuals with PTPN11 Mutations. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-0986-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1507\/endocrj.EJ18-0564","article-title":"Genotype-Phenotype Correlation Analysis in Japanese Patients with Noonan Syndrome","volume":"66","author":"Shoji","year":"2019","journal-title":"Endocr. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/bdr2.1659","article-title":"Noonan Syndrome with Multiple Giant Cell Lesions, Management and Treatment with Surgery and Interferon Alpha-2a Therapy: Case Report","volume":"112","author":"Moreno","year":"2020","journal-title":"Birth Defects Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/ejhg.2009.44","article-title":"SOS1 and PTPN11 Mutations in Five Cases of Noonan Syndrome with Multiple Giant Cell Lesions","volume":"17","author":"Beneteau","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00431-024-05825-8","article-title":"Clinical Features and Molecular Genetics of Patients with RASopathies: Expanding the Phenotype with Rare Genes and Novel Variants","volume":"184","author":"Vuran","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/ejhg.2014.220","article-title":"Expanding the Mutational Spectrum of LZTR1 in Schwannomatosis","volume":"23","author":"Paganini","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/cge.13533","article-title":"Delineation of Dominant and Recessive Forms of LZTR1-associated Noonan Syndrome","volume":"95","author":"Pagnamenta","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/ajmg.a.61445","article-title":"Providing More Evidence on LZTR1 Variants in Noonan Syndrome Patients","volume":"182","author":"Chinton","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1159\/000502741","article-title":"LZTR1: Genotype Expansion in Noonan Syndrome","volume":"92","author":"Argente","year":"2019","journal-title":"Horm. Res. Paediatr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/s41431-022-01086-x","article-title":"ERN GENTURIS Clinical Practice Guidelines for the Diagnosis, Treatment, Management and Surveillance of People with Schwannomatosis","volume":"30","author":"Evans","year":"2022","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1002\/ajmg.a.36098","article-title":"Expanding the SHOC2 Mutation Associated Phenotype of Noonan Syndrome with Loose Anagen Hair: Structural Brain Anomalies and Myelofibrosis","volume":"161","author":"Gripp","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_40","first-page":"330","article-title":"Clinical and Molecular Characterization of Children with Noonan Syndrome and Other RASopathies in Argentina","volume":"117","author":"Chinton","year":"2019","journal-title":"Arch. Argent. Pediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1002\/humu.24001","article-title":"ZMYND11-related Syndromic Intellectual Disability: 16 Patients Delineating and Expanding the Phenotypic Spectrum","volume":"41","author":"Yates","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.hfc.2021.07.004","article-title":"Hypertrophic Cardiomyopathy in RASopathies: Diagnosis, Clinical Characteristics, Prognostic Implications, and Management","volume":"18","author":"Lioncino","year":"2022","journal-title":"Heart Fail. Clin."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ilic, N., Krasic, S., Maric, N., Gasic, V., Krstic, J., Cvetkovic, D., Miljkovic, V., Zec, B., Maver, A., and Vukomanovic, V. (2024). Noonan Syndrome: Relation of Genotype to Cardiovascular Phenotype\u2014A Multi-Center Retrospective Study. Genes, 15.","DOI":"10.3390\/genes15111463"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/gim.2017.249","article-title":"Autosomal Recessive Noonan Syndrome Associated with Biallelic LZTR1 Variants","volume":"20","author":"Johnston","year":"2018","journal-title":"Genet. Med."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/8\/1207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:11:48Z","timestamp":1776744708000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/8\/1207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":44,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["diagnostics16081207"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16081207","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]}}}