noonan syndrome

Summary

Summary: A genetically heterogeneous, multifaceted disorder characterized by short stature, webbed neck, ptosis, skeletal malformations, hypertelorism, hormonal imbalance, CRYPTORCHIDISM, multiple cardiac abnormalities (most commonly including PULMONARY VALVE STENOSIS), and some degree of INTELLECTUAL DISABILITY. The phenotype bears similarities to that of TURNER SYNDROME that occurs only in females and has its basis in a 45, X karyotype abnormality. Noonan syndrome occurs in both males and females with a normal karyotype (46,XX and 46,XY). Mutations in a several genes (PTPN11, KRAS, SOS1, NF1 and RAF1) have been associated the the NS phenotype. Mutations in PTPN11 are the most common. LEOPARD SYNDROME, a disorder that has clinical features overlapping those of Noonan Syndrome, is also due to mutations in PTPN11. In addition, there is overlap with the syndrome called neurofibromatosis-Noonan syndrome due to mutations in NF1.

Top Publications

  1. Zhang W, Chan R, Chen H, Yang Z, He Y, Zhang X, et al. Negative regulation of Stat3 by activating PTPN11 mutants contributes to the pathogenesis of Noonan syndrome and juvenile myelomonocytic leukemia. J Biol Chem. 2009;284:22353-63 pubmed publisher
    b>Noonan syndrome (NS) is an autosomal dominant congenital disorder characterized by multiple birth defects including heart defects and myeloproliferative disease (MPD)...
  2. Bertola D, Pereira A, Brasil A, Albano L, Kim C, Krieger J. Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene. J Hum Genet. 2007;52:521-6 pubmed
    ..a patient presenting the clinical features typical of Costello syndrome and the additional findings seen in Noonan syndrome. This description emphasizes that a subset of patients with Costello syndrome could harbor mutations in other ..
  3. Mutesa L, Pierquin G, Janin N, Segers K, Thomée C, Provenzi M, et al. Germline PTPN11 missense mutation in a case of Noonan syndrome associated with mediastinal and retroperitoneal neuroblastic tumors. Cancer Genet Cytogenet. 2008;182:40-2 pubmed publisher
    b>Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart defects, and predisposition to malignant tumors...
  4. Rani D, Dhandapany P, Nallari P, Govindaraj P, Singh L, Thangaraj K. Mitochondrial DNA haplogroup 'R' is associated with Noonan syndrome of south India. Mitochondrion. 2010;10:166-73 pubmed publisher
    Mutations in PTPN11 gene was responsible for approximately 50% of the Noonan syndrome (NS), however, we did not find any mutation in PTPN11 in any of seven NS patients analysed...
  5. Lee D, Portnoy S, Hill P, Gillberg C, Patton M. Psychological profile of children with Noonan syndrome. Dev Med Child Neurol. 2005;47:35-8 pubmed
    A cohort of 48 children with Noonan syndrome, with a mean age of 9 years 10 months (SD 3y 7mo; 28 males, 20 females), was recruited from a national study...
  6. Razzaque M, Komoike Y, Nishizawa T, Inai K, Furutani M, Higashinakagawa T, et al. Characterization of a novel KRAS mutation identified in Noonan syndrome. Am J Med Genet A. 2012;158A:524-32 pubmed publisher
    b>Noonan syndrome (NS) is the most common non-chromosomal syndrome seen in children and is characterized by short stature, dysmorphic facial features, chest deformity, a wide range of congenital heart defects and developmental delay of ..
  7. Schubbert S, Zenker M, Rowe S, Böll S, Klein C, Bollag G, et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet. 2006;38:331-6 pubmed
    b>Noonan syndrome (MIM 163950) is characterized by short stature, facial dysmorphism and cardiac defects. Heterozygous mutations in PTPN11, which encodes SHP-2, cause approximately 50% of cases of Noonan syndrome...
  8. Gauthier A, Furstoss O, Araki T, Chan R, Neel B, Kaplan D, et al. Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan syndrome. Neuron. 2007;54:245-62 pubmed
    ..genetic mutations resulting in constitutive activation of the protein tyrosine phosphatase SHP-2 cause Noonan Syndrome (NS), which is associated with learning disabilities and mental retardation...
  9. Tartaglia M, Gelb B. Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2005;6:45-68 pubmed
    b>Noonan syndrome is a pleiomorphic autosomal dominant disorder with short stature, facial dysmorphia, webbed neck, and heart defects...

More Information

Publications98

  1. Chantrain C, Jijon P, De Raedt T, Vermylen C, Poirel H, Legius E, et al. Therapy-related acute myeloid leukemia in a child with Noonan syndrome and clonal duplication of the germline PTPN11 mutation. Pediatr Blood Cancer. 2007;48:101-4 pubmed
    A 4-year-old girl with Noonan syndrome (NS) and constitutive PTPN11 mutation presented with stage 4 neuroblastoma and was treated by intensive chemotherapy...
  2. Ferreira L, Souza S, Arnhold I, Mendonca B, Jorge A. PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. J Clin Endocrinol Metab. 2005;90:5156-60 pubmed
    The cause of growth impairment in Noonan syndrome (NS) remains unclear...
  3. Chen P, 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–associated Sos1 mutation. J Clin Invest. 2010;120:4353-65 pubmed publisher
    b>Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, unique facial features, and congenital heart disease...
  4. Araki T, Chan G, Newbigging S, Morikawa L, Bronson R, Neel B. Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformation. Proc Natl Acad Sci U S A. 2009;106:4736-41 pubmed publisher
    b>Noonan syndrome (NS), the most common single-gene cause of congenital heart disease, is an autosomal dominant disorder that also features proportionate short stature, facial abnormalities, and an increased risk of myeloproliferative ..
  5. Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, et al. SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations. Hum Mutat. 2011;32:760-72 pubmed publisher
    b>Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth...
  6. Noonan J. Noonan syndrome and related disorders: alterations in growth and puberty. Rev Endocr Metab Disord. 2006;7:251-5 pubmed
    b>Noonan syndrome is a relatively common multiple malformation syndrome with characteristic facies, short stature and congenital heart disease, most commonly pulmonary stenosis (Noonan, Clin Pediatr, 33:548-555, 1994)...
  7. Nyström A, Ekvall S, Stromberg B, Holmstrom G, Thuresson A, Anneren G, et al. A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins. Acta Paediatr. 2009;98:693-8 pubmed publisher
    The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis...
  8. Nyström A, Ekvall S, Allanson J, Edeby C, Elinder M, Holmstrom G, et al. Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1. Clin Genet. 2009;76:524-34 pubmed publisher
    b>Noonan syndrome (NS) and neurofibromatosis type I (NF1) belong to a group of clinically related disorders that share a common pathogenesis, dysregulation of the RAS-MAPK pathway...
  9. Stewart R, Sanda T, Widlund H, Zhu S, Swanson K, Hurley A, et al. Phosphatase-dependent and -independent functions of Shp2 in neural crest cells underlie LEOPARD syndrome pathogenesis. Dev Cell. 2010;18:750-62 pubmed publisher
    ..Paradoxically, Noonan syndrome mutations increase SHP2 phosphatase activity, while LEOPARD syndrome mutants are catalytically impaired, ..
  10. Wu X, Yin J, Simpson J, Kim K, Gu S, Hong J, et al. Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants. Mol Cell Biol. 2012;32:3872-90 pubmed publisher
    b>Noonan syndrome (NS) is a relatively common autosomal dominant disorder characterized by congenital heart defects, short stature, and facial dysmorphia...
  11. Araki T, Mohi M, Ismat F, Bronson R, Williams I, Kutok J, et al. Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nat Med. 2004;10:849-57 pubmed
    b>Noonan syndrome is a common human autosomal dominant birth defect, characterized by short stature, facial abnormalities, heart defects and possibly increased risk of leukemia...
  12. Yoshida R, Ogata T, Masawa N, Nagai T. Hepatoblastoma in a Noonan syndrome patient with a PTPN11 mutation. Pediatr Blood Cancer. 2008;50:1274-6 pubmed publisher
    Although Noonan syndrome (NS) is occasionally associated with embryonal solid tumors, there has been no report of hepatoblastoma in NS...
  13. Nakamura T, Gulick J, Pratt R, Robbins J. Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations. Proc Natl Acad Sci U S A. 2009;106:15436-41 pubmed publisher
    A gain of function mutation in SHP2, a protein phosphatase encoded by PTPN11, causes Noonan syndrome (NS), which is characterized in part by developmental deficits in both the cardiac and skull fields...
  14. Shchelochkov O, Patel A, Weissenberger G, Chinault A, Wiszniewska J, Fernandes P, et al. Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome. Am J Med Genet A. 2008;146A:1042-8 pubmed publisher
    b>Noonan syndrome is an autosomal dominant disorder with an estimated incidence of 1 in 1,000 to 1 in 2,500 live births...
  15. De Luca A, Bottillo I, Sarkozy A, Carta C, Neri C, Bellacchio E, et al. NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome. Am J Hum Genet. 2005;77:1092-101 pubmed
    Neurofibromatosis type 1 (NF1) demonstrates phenotypic overlap with Noonan syndrome (NS) in some patients, which results in the so-called neurofibromatosis-Noonan syndrome (NFNS)...
  16. Hanna N, Parfait B, Talaat I, Vidaud M, Elsedfy H. SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome. Clin Genet. 2009;75:568-71 pubmed publisher
    Noonan-like/multiple giant cell lesion syndrome is a rare condition with phenotypic overlap with Noonan syndrome (NS) and cherubism...
  17. Sherman C, Ali Nazir A, Gonzales Gomez I, Finlay J, Dhall G. Primary mixed glioneuronal tumor of the central nervous system in a patient with noonan syndrome: a case report and review of the literature. J Pediatr Hematol Oncol. 2009;31:61-4 pubmed publisher
    b>Noonan syndrome is an autosomal dominant condition with variable phenotypic expression...
  18. Ekvall S, Hagenäs L, Allanson J, Anneren G, Bondeson M. Co-occurring SHOC2 and PTPN11 mutations in a patient with severe/complex Noonan syndrome-like phenotype. Am J Med Genet A. 2011;155A:1217-24 pubmed publisher
    b>Noonan syndrome (NS) is a heterogeneous disorder caused by activating mutations in the RAS-MAPK signaling pathway...
  19. Tartaglia M, Pennacchio L, Zhao C, Yadav K, Fodale V, Sarkozy A, et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet. 2007;39:75-9 pubmed
    b>Noonan syndrome is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart defects and skeletal anomalies...
  20. Beier A, Barrett R, Burke K, Kole B, Soo T. Leopard syndrome and Chiari type I malformation: a case report and review of the literature. Neurologist. 2009;15:37-9 pubmed publisher
    ..The patient underwent a suboccipital craniectomy with C1 laminectomy and duraplasty. His symptoms quickly resolved and his PEG tube was removed...
  21. Nava C, Hanna N, Michot C, Pereira S, Pouvreau N, Niihori T, et al. Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome. J Med Genet. 2007;44:763-71 pubmed
    Cardio-facio-cutaneous (CFC) syndrome, Noonan syndrome (NS), and Costello syndrome (CS) are clinically related developmental disorders that have been recently linked to mutations in the RAS/MEK/ERK signalling pathway...
  22. Longoni M, Moncini S, Cisternino M, Morella I, Ferraiuolo S, Russo S, et al. Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations. Am J Med Genet A. 2010;152A:2176-84 pubmed publisher
    b>Noonan syndrome is a genetic condition characterized by congenital heart defects, short stature, and characteristic facial features...
  23. Karow A, Steinemann D, Göhring G, Hasle H, Greiner J, Harila Saari A, et al. Clonal duplication of a germline PTPN11 mutation due to acquired uniparental disomy in acute lymphoblastic leukemia blasts from a patient with Noonan syndrome. Leukemia. 2007;21:1303-5 pubmed
  24. Ko J, Kim J, Kim G, Yoo H. PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome. J Hum Genet. 2008;53:999-1006 pubmed publisher
    After 2006, germline mutations in the KRAS, SOS1, and RAF1 genes were reported to cause Noonan syndrome (NS), in addition to the PTPN11 gene, and now we can find the etiology of disease in approximately 60-70% of NS cases...
  25. Altamirano E, Drut R. Arrhythmogenic cardiomyopathy in a patient with Noonan syndrome. Fetal Pediatr Pathol. 2010;29:158-64 pubmed publisher
    ..We report an 11-year-old boy with Noonan syndrome, ventricular arrhythmias, and an ultrasound depicting hypertrophy of the ventricular septum with subaortic ..
  26. Molzan M, Schumacher B, Ottmann C, Baljuls A, Polzien L, Weyand M, et al. Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling. Mol Cell Biol. 2010;30:4698-711 pubmed publisher
    ..In one of those disorders, namely, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259), a regulatory site for inhibition by 14-3-3 proteins...
  27. Yoon S, Choi S, Eboreime J, Gelb B, Calabrese P, Arnheim N. Age-dependent germline mosaicism of the most common noonan syndrome mutation shows the signature of germline selection. Am J Hum Genet. 2013;92:917-26 pubmed publisher
    b>Noonan syndrome (NS) is among the most common Mendelian genetic diseases (?1/2,000 live births). Most cases (50%-84%) are sporadic, and new mutations are virtually always paternally derived...
  28. Carta C, Pantaleoni F, Bocchinfuso G, Stella L, Vasta I, Sarkozy A, et al. Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Am J Hum Genet. 2006;79:129-35 pubmed
    b>Noonan syndrome (NS) is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart disease, and multiple skeletal and hematologic defects...
  29. Wang S, Yu W, Zhang W, McCrae K, Neel B, Qu C. Noonan syndrome/leukemia-associated gain-of-function mutations in SHP-2 phosphatase (PTPN11) enhance cell migration and angiogenesis. J Biol Chem. 2009;284:913-20 pubmed publisher
    ..in SHP-2 phosphatase (PTPN11) that cause hyperactivation of its catalytic activity have been identified in Noonan syndrome and various childhood leukemias...
  30. Ranke M. Noonan syndrome: growth to growth hormone - the experience of observational studies. Horm Res. 2009;72 Suppl 2:36-40 pubmed publisher
    Short stature is one of the key features of Noonan syndrome (NS). Attempts have therefore been made to improve height by means of recombinant human growth hormone (rhGH) treatment...
  31. Zenker M. Genetic and pathogenetic aspects of Noonan syndrome and related disorders. Horm Res. 2009;72 Suppl 2:57-63 pubmed publisher
    b>Noonan syndrome (NS) and the clinically overlapping disorders cardio-facio-cutaneous syndrome, LEOPARD syndrome, Costello syndrome and Neurofibromatosis-Noonan syndrome share the clinical features of short stature, the same spectrum of ..
  32. Lopez Rangel E, Malleson P, Lirenman D, Roa B, Wiszniewska J, Lewis M. Systemic lupus erythematosus and other autoimmune disorders in children with Noonan syndrome. Am J Med Genet A. 2005;139:239-42 pubmed
  33. Jongmans M, Hoogerbrugge P, Hilkens L, Flucke U, van der Burgt I, Noordam K, et al. Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma. Genes Chromosomes Cancer. 2010;49:635-41 pubmed publisher
    b>Noonan Syndrome (NS) is an autosomal dominant condition characterized by short stature, facial dysmorphisms, and congenital heart defects, and is caused by mutations in either PTPN11, KRAS, NRAS, SHOC2, RAF1, or SOS1...
  34. Nyström A, Ekvall S, Berglund E, Bjorkqvist M, Braathen G, Duchen K, et al. Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders. J Med Genet. 2008;45:500-6 pubmed publisher
    b>Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFC) are related disorders associated with disrupted RAS/RAF/MEK/ERK signalling...
  35. Bufalino A, Carrera M, Carlos R, Coletta R. Giant cell lesions in noonan syndrome: case report and review of the literature. Head Neck Pathol. 2010;4:174-7 pubmed publisher
    Noonan-like/multiple giant cell lesion syndrome (NS/MGCLS) is a rare condition with phenotypic overlap with Noonan syndrome (NS). Once thought to be a specific and separate entity, it is now suggested to be a variant of the NS spectrum...
  36. Krenz M, Gulick J, Osinska H, Colbert M, Molkentin J, Robbins J. Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc Natl Acad Sci U S A. 2008;105:18930-5 pubmed publisher
    b>Noonan syndrome (NS) is the most common nonchromosomal genetic disorder associated with cardiovascular malformations. The most prominent cardiac defects in NS are pulmonary valve stenosis and hypertrophic cardiomyopathy...
  37. Neumann T, 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. Eur J Hum Genet. 2009;17:420-5 pubmed publisher
    b>Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade...
  38. Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am J Hum Genet. 2006;78:279-90 pubmed
    Germline mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome (NS) and the clinically related LEOPARD syndrome (LS), whereas somatic mutations in the same gene contribute to leukemogenesis...
  39. Croonen E, Nillesen W, Stuurman K, Oudesluijs G, van de Laar I, Martens L, et al. Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings. Eur J Hum Genet. 2013;21:936-42 pubmed publisher
    In recent studies on prenatal testing for Noonan syndrome (NS) in fetuses with an increased nuchal translucency (NT) and a normal karyotype, mutations have been reported in 9-16% of cases...
  40. Kraoua L, Journel H, Bonnet P, Amiel J, Pouvreau N, Baumann C, et al. Constitutional NRAS mutations are rare among patients with Noonan syndrome or juvenile myelomonocytic leukemia. Am J Med Genet A. 2012;158A:2407-11 pubmed publisher
    Recently, germline mutations of NRAS have been shown to be associated with Noonan syndrome (NS), a relatively common developmental disorder characterized by short stature, congenital heart disease, and distinctive facial features...
  41. Oishi K, Gaengel K, Krishnamoorthy S, Kamiya K, Kim I, Ying H, et al. Transgenic Drosophila models of Noonan syndrome causing PTPN11 gain-of-function mutations. Hum Mol Genet. 2006;15:543-53 pubmed
    Mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP-2, causes Noonan syndrome (NS), an autosomal dominant disorder with pleomorphic developmental abnormalities...
  42. Gremer L, Merbitz Zahradnik T, Dvorsky R, Cirstea I, Kratz C, Zenker M, et al. Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders. Hum Mutat. 2011;32:33-43 pubmed publisher
    ..Germline KRAS mutations were shown recently to be associated with developmental disorders, including Noonan syndrome (NS), cardio-facio-cutaneous syndrome (CFCS), and Costello syndrome (CS)...
  43. Reynolds D, Rubin S, Fox J, Kodsi S. Ocular manifestations of Noonan syndrome in the pediatric patient. J AAPOS. 2004;8:282-3 pubmed
    b>Noonan syndrome is a rare syndrome with both ocular findings and multiple organ involvement...
  44. Kontaridis M, Swanson K, David F, Barford D, Neel B. PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. J Biol Chem. 2006;281:6785-92 pubmed
    ..Like the more common Noonan syndrome (NS), LS is caused by germ line missense mutations in PTPN11, encoding the protein-tyrosine phosphatase Shp2...
  45. Jafarov T, Ferimazova N, Reichenberger E. Noonan-like syndrome mutations in PTPN11 in patients diagnosed with cherubism. Clin Genet. 2005;68:190-1 pubmed
  46. Nakagawa M, Kinouchi K, Matsunami K, Ono R, Miyagawa Y, Ueda D, et al. [Anesthetic management of a child with Noonan syndrome and hypertrophic obstructive cardiomyopathy]. Masui. 2006;55:92-5 pubmed
    b>Noonan syndrome is characterized by facial, skeletal and cardiovascular anomalies...
  47. Martinelli S, De Luca A, Stellacci E, Rossi C, Checquolo S, Lepri F, et al. Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype. Am J Hum Genet. 2010;87:250-7 pubmed publisher
    ..ubiquitin ligase activity, can underlie a phenotype with clinical features fitting or partially overlapping Noonan syndrome (NS), the most common condition of this disease family...
  48. Dinopoulos A, Papadopoulou A, Manta P, Kekou K, Kanelopoulos T, Fretzayas A, et al. Coinheritance of Noonan syndrome and Becker muscular dystrophy. Neuromuscul Disord. 2010;20:61-3 pubmed publisher
    We describe for the first time a case of a 9-year old boy with co-existence of dystrophinopathy and Noonan syndrome (NS)...
  49. Keilhack H, David F, McGregor M, Cantley L, Neel B. Diverse biochemical properties of Shp2 mutants. Implications for disease phenotypes. J Biol Chem. 2005;280:30984-93 pubmed
    ..phosphatase Shp2 (PTPN11) underlie half of the cases of the autosomal dominant genetic disorder Noonan syndrome, and somatic Shp2 mutations are found in several hematologic and solid malignancies...
  50. Cordeddu V, Di Schiavi E, Pennacchio L, Ma ayan A, Sarkozy A, Fodale V, et al. Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair. Nat Genet. 2009;41:1022-6 pubmed publisher
    ..These results document the first example of an acquired N-terminal lipid modification of a protein causing human disease...
  51. Tidyman W, Rauen K. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Genet Dev. 2009;19:230-6 pubmed publisher
    ..Here we review the clinical and underlying molecular basis for each of these syndromes...
  52. Lee S, Cooper J. Noonan syndrome with giant cell lesions. Int J Paediatr Dent. 2005;15:140-5 pubmed
    b>Noonan syndrome is characterised by short stature, unusual facies, congenital heart disease, chest deformity and mild mental retardation. It may be sporadic or inherited as an autosomal dominant trait and occurs between one in 1000-2500...
  53. Jorge A, Malaquias A, Arnhold I, Mendonca B. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Horm Res. 2009;71:185-93 pubmed publisher
    b>Noonan syndrome (NS) is one of the most common syndromes transmitted by a mendelian mode...
  54. Prada C, Zarate Y, Hagenbuch S, Lovell A, Schorry E, Hopkin R. Lethal presentation of neurofibromatosis and Noonan syndrome. Am J Med Genet A. 2011;155A:1360-6 pubmed publisher
    Neurofibromatosis type 1 and Noonan syndrome are both common genetic disorders with autosomal dominant inheritance...
  55. Pandit B, Sarkozy A, Pennacchio L, Carta C, Oishi K, Martinelli S, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007;39:1007-12 pubmed
    ..Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases...
  56. Allanson J. Noonan syndrome. Am J Med Genet C Semin Med Genet. 2007;145C:274-9 pubmed
    b>Noonan syndrome is a common autosomal dominant condition caused by multiple genes in the RasMAPK pathway. The adult phenotype can be extremely subtle, and many adults are diagnosed only after the birth of a more obviously affected child...
  57. Asokan S, Muthu M, Rathna Prabhu V. Noonan syndrome: a case report. J Indian Soc Pedod Prev Dent. 2007;25:144-7 pubmed
    b>Noonan syndrome is a developmental disorder characterized by facial dysmorphia, short stature, cardiac defects and skeletal malformations...
  58. Jopling C, van Geemen D, den Hertog J. Shp2 knockdown and Noonan/LEOPARD mutant Shp2-induced gastrulation defects. PLoS Genet. 2007;3:e225 pubmed
    ..The finding that defective Shp2 signaling induced cell movement defects as early as gastrulation may have implications for the monitoring and diagnosis of Noonan and LEOPARD syndrome...
  59. Douvoyiannis M, Belamarich P, Litman N. Parotitis and kawasaki disease in a child with Noonan syndrome. Pediatr Infect Dis J. 2008;27:89-90 pubmed
  60. Wu X, Simpson J, Hong J, Kim K, Thavarajah N, Backx P, 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;121:1009-25 pubmed publisher
    ..b>Noonan syndrome (NS) is one of several autosomal-dominant conditions known as RASopathies, which are caused by mutations in ..
  61. Runtuwene V, van Eekelen M, Overvoorde J, Rehmann H, Yntema H, Nillesen W, et al. Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects. Dis Model Mech. 2011;4:393-9 pubmed publisher
    b>Noonan syndrome is a relatively common developmental disorder that is characterized by reduced growth, wide-set eyes and congenital heart defects...
  62. Tofil N, Winkler M, Watts R, Noonan J. The use of recombinant factor VIIa in a patient with Noonan syndrome and life-threatening bleeding. Pediatr Crit Care Med. 2005;6:352-4 pubmed
    To present a case report of a patient with Noonan syndrome who developed life-threatening gastrointestinal bleeding shortly after cardiac surgery that was successfully treated with recombinant factor VIIa.
  63. Edwards P, Fox J, Fantasia J, Goldberg J, Kelsch R. Bilateral central giant cell granulomas of the mandible in an 8-year-old girl with Noonan syndrome (Noonan-like/multiple giant cell lesion syndrome). Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99:334-40 pubmed
    ..Characteristic facial features and a history of pulmonary stenosis led us to suspect a diagnosis of Noonan syndrome. A medical geneticist confirmed this. This case report will discuss the salient features of this diagnosis.
  64. Binder G, Neuer K, Ranke M, Wittekindt N. PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. J Clin Endocrinol Metab. 2005;90:5377-81 pubmed
    b>Noonan syndrome is frequently associated with an unclear disturbance of GH secretion...
  65. Lee J, Tartaglia M, Gelb B, Fridrich K, Sachs S, Stratakis C, et al. Phenotypic and genotypic characterisation of Noonan-like/multiple giant cell lesion syndrome. J Med Genet. 2005;42:e11 pubmed
  66. Binder G. Response to growth hormone in short children with Noonan syndrome: correlation to genotype. Horm Res. 2009;72 Suppl 2:52-6 pubmed publisher
    Short stature is a major characteristic of Noonan syndrome (NS), the biological basis of which is not yet clear...
  67. Narumi Y, Aoki Y, Niihori T, Sakurai M, Cave H, Verloes A, et al. Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome. J Hum Genet. 2008;53:834-41 pubmed publisher
    b>Noonan syndrome (NS) and cardio-facio-cutaneous (CFC) syndrome are autosomal dominant disorders characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and mental retardation...
  68. Lee I, Pecinova A, Pecina P, Neel B, Araki T, Kucherlapati R, et al. A suggested role for mitochondria in Noonan syndrome. Biochim Biophys Acta. 2010;1802:275-83 pubmed publisher
    b>Noonan syndrome (NS) is an autosomal dominant disorder, and a main feature is congenital heart malformation...
  69. Gelb B, Tartaglia M. Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. Hum Mol Genet. 2006;15 Spec No 2:R220-6 pubmed
    b>Noonan syndrome is a relatively common, genetically heterogeneous Mendelian trait with a pleiomorphic phenotype...
  70. Emral M, Akcam M. Noonan syndrome: a case report. J Oral Sci. 2009;51:301-6 pubmed
    Cranio-dento-facial findings in a case of Noonan syndrome in a 13-year, 3-month-old male are reported. Oral examination of the patient revealed a narrow, high arched palate, malocclusion and congenitally missing teeth...
  71. Zenker M, Lehmann K, Schulz A, Barth H, Hansmann D, Koenig R, et al. Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. J Med Genet. 2007;44:131-5 pubmed
    b>Noonan syndrome, cardio-facio-cutaneous syndrome (CFC) and Costello syndrome constitute a group of developmental disorders with an overlapping pattern of congenital anomalies...
  72. Thiel C, Wilken M, Zenker M, Sticht H, Fahsold R, Gusek Schneider G, et al. Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. Am J Med Genet A. 2009;149A:1263-7 pubmed publisher
    Neurofibromatosis-Noonan syndrome (NFNS), an entity which combines both features of Noonan syndrome (NS) and neurofibromatosis type 1 (NF1), was etiologically unresolved until recent reports demonstrated NF1 mutations in the majority of ..
  73. Sznajer Y, Keren B, Baumann C, Pereira S, Alberti C, Elion J, et al. The spectrum of cardiac anomalies in Noonan syndrome as a result of mutations in the PTPN11 gene. Pediatrics. 2007;119:e1325-31 pubmed
    b>Noonan syndrome is a clinically homogeneous but genetically heterogeneous condition. Type 1 Noonan syndrome is defined by the presence of a mutation in the PTPN11 gene, which is found in approximately 40% of the cases...
  74. Beneteau C, Cave H, Moncla A, Dorison N, Munnich A, Verloes A, et al. SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions. Eur J Hum Genet. 2009;17:1216-21 pubmed publisher
    We report five cases of multiple giant cell lesions in patients with typical Noonan syndrome. Such association has frequently been referred to as Noonan-like/multiple giant cell (NL/MGCL) syndrome before the molecular definition of ..
  75. Zenker M, Horn D, Wieczorek D, Allanson J, Pauli S, van der Burgt I, et al. SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. J Med Genet. 2007;44:651-6 pubmed
    ..genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS)...
  76. Sidwell R, Rouse P, Owen R, Green J. Granular cell tumor of the scrotum in a child with Noonan syndrome. Pediatr Dermatol. 2008;25:341-3 pubmed publisher
    ..We report a granular cell tumor of the scrotum in a child with Noonan syndrome, known to have a mutation in the PTPN11 gene...
  77. Osio D, Dahlgren J, Wikland K, Westphal O. Improved final height with long-term growth hormone treatment in Noonan syndrome. Acta Paediatr. 2005;94:1232-7 pubmed
    To assess whether children with Noonan syndrome on long-term growth hormone (GH) therapy improve their final height to near mid-parental height.
  78. Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, et al. Genotype-phenotype correlations in Noonan syndrome. J Pediatr. 2004;144:368-74 pubmed
    To study genotype-phenotype correlations in a cohort of clinically well-characterized pediatric patients with Noonan syndrome (NS)...
  79. Bertola D, Pereira A, de Oliveira P, Kim C, Krieger J. Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation. Am J Med Genet A. 2004;130A:378-83 pubmed
    b>Noonan syndrome (NS) is an autosomal dominant disorder comprising short stature, facial dysmorphism, short and/or webbed neck, heart defects, and cryptorchidism in males...
  80. Choudhry K, Grover M, Tran A, O Brian Smith E, Ellis K, Lee B. Decreased bone mineralization in children with Noonan syndrome: another consequence of dysregulated RAS MAPKinase pathway?. Mol Genet Metab. 2012;106:237-40 pubmed publisher
    b>Noonan syndrome (NS) is a disorder of RAS- mitogen activated protein kinase (MAPK) pathway with clinical features of skeletal dysplasia...
  81. Toureno L, Park J. Atypical orofacial conditions in Noonan syndrome: a case report. J Clin Pediatr Dent. 2011;36:197-202 pubmed
    b>Noonan syndrome (NS) is a relatively common condition characterized by chest deformation, congenital heart disease, short stature and distinctive facial features...
  82. Razzaque M, 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;39:1013-7 pubmed
    b>Noonan syndrome is characterized by short stature, facial dysmorphia and a wide spectrum of congenital heart defects. Mutations of PTPN11, KRAS and SOS1 in the RAS-MAPK pathway cause approximately 60% of cases of Noonan syndrome...
  83. Lee B, Kim J, Jin H, Kim G, Choi J, Yoo H. Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. J Pediatr. 2011;159:1029-35 pubmed publisher
    To investigate mutation spectrums and their correlations to phenotypes in Noonan syndrome (NS) and NS-related disorders that share functional alterations of the Ras-mitogen-activated protein kinase pathway.
  84. Bastida P, Garcia Minaur S, Ezquieta B, Dapena J, Sanchez de Toledo J. Myeloproliferative disorder in Noonan syndrome. J Pediatr Hematol Oncol. 2011;33:e43-5 pubmed publisher
    Children with Noonan syndrome (NS) are at increased risk of developing juvenile myelomonocytic leukemia (JMML) or a myeloproliferative disorder associated with NS (MPD/NS) resembling JMML in the first weeks of life; whereas JMML is an ..
  85. Yalcin B, Yalcçin B, Tamer E, Gur G, Oztas P, Polat M, et al. Neurofibromatosis 1/Noonan syndrome associated with Hashimoto's thyroiditis and vitiligo. Acta Derm Venereol. 2006;86:80-1 pubmed
  86. Cirstea I, Kutsche K, Dvorsky R, Gremer L, Carta C, Horn D, et al. A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet. 2010;42:27-9 pubmed publisher
    b>Noonan syndrome, a developmental disorder characterized by congenital heart defects, reduced growth, facial dysmorphism and variable cognitive deficits, is caused by constitutional dysregulation of the RAS-MAPK signaling pathway...
  87. Allanson J, Bohring A, Dörr H, Dufke A, Gillessen Kaesbach G, Horn D, et al. The face of Noonan syndrome: Does phenotype predict genotype. Am J Med Genet A. 2010;152A:1960-6 pubmed publisher
    The facial photographs of 81 individuals with Noonan syndrome, from infancy to adulthood, have been evaluated by two dysmorphologists (JA and MZ), each of whom has considerable experience with disorders of the Ras/MAPK pathway...
  88. Eminaga S, Bennett A. Noonan syndrome-associated SHP-2/Ptpn11 mutants enhance SIRPalpha and PZR tyrosyl phosphorylation and promote adhesion-mediated ERK activation. J Biol Chem. 2008;283:15328-38 pubmed publisher
    b>Noonan syndrome (NS) is an autosomal dominant disorder that is associated with multiple developmental abnormalities...
  89. Krenz M, Yutzey K, Robbins J. Noonan syndrome mutation Q79R in Shp2 increases proliferation of valve primordia mesenchymal cells via extracellular signal-regulated kinase 1/2 signaling. Circ Res. 2005;97:813-20 pubmed
    ..the role of extracellular signal-regulated kinase (ERK) 1/2 activation in valve primordia expressing the Noonan syndrome mutation Q79R-Shp2...