Medscape is available in 5 Language Editions – Choose your Edition here.


Noonan Syndrome Workup

  • Author: Margaret M McGovern, MD, PhD; Chief Editor: Luis O Rohena, MD  more...
Updated: Jun 13, 2016

Approach Considerations

All patients with Noonan syndrome should be evaluated to determine which disease manifestations they display. A complete physical and neurologic examination should be performed, and a genetics consultation should be sought. In addition, the following assessments should be made at the time of diagnosis:

  • Cardiac evaluation: Including echocardiographic and electrocardiographic assessment
  • Ophthalmologic and audiologic evaluation
  • Coagulation screen
  • Renal ultrasonographic examination
  • Developmental assessment

Before any patient with Noonan syndrome can undergo a surgical procedure, a full hematologic workup must be performed.


Laboratory Studies

Bleeding diatheses are common among patients with Noonan syndrome. The most frequent abnormality is factor XI deficiency, but various disorders have been reported in patients with Noonan syndrome. A complete blood count (CBC) with platelet count, coagulation profile, and measurement of factor XI level should be obtained at a minimum. Moreover, before any patient with Noonan syndrome can undergo a surgical procedure, a full hematologic workup must be performed.

If full phenotypic expression is not apparent, karyotyping may be necessary. Mutation analysis may confirm the diagnosis of Noonan syndrome, but failure to identify a germline mutation in any of the associated genes does not rule out the disorder; this entity remains a clinical diagnosis.

Many individuals with Noonan syndrome have reduced insulinlike growth factor-1 (IGF-1) and IGF-binding protein 3, but these tests are not diagnostic of the syndrome itself.


Imaging Studies

Appropriate imaging studies in Noonan syndrome include the following:

  • Echocardiography
  • Renal ultrasonography
  • Brain and cervical spine magnetic resonance imaging (MRI): If neurologic symptoms are present
  • Radiography: To examine the chest and back if abnormalities are present [1] and to evaluate the patient for Noonan-like/multiple giant cell lesion syndrome (NS/MGCLS)

Other Tests

Any child suspected of having Noonan syndrome requires a detailed cardiac workup. This includes electrocardiography, echocardiography, and consultation with a pediatric cardiologist.

Assessment of development is necessary to identify any delays and allow for intervention. Full-scale intelligence quotient (IQ) ranges from 48-130, with a mean of 86.1 (approximately one standard deviation [SD] below the general population mean). Approximately 25% of patients with Noonan syndrome have mental retardation. A study by Roelofs et al found that in persons with Noonan syndrome, full-scale and performance IQs saw significant improvement in adult scores compared with childhood values, with performance IQ reaching normal levels. However, verbal IQ did not advance proportionately to performance IQ by adulthood. The investigators suggested that the improvement in performance IQ in individuals with Noonan syndrome points to a developmental delay in executive functioning that is outgrown in adulthood. However, maturation of motor skills was also suggested as a reason for the improvement. The study included 16 patients, whose intelligence was evaluated in childhood and adulthood.[17]

The incidence of progressive high-frequency sensorineural hearing loss may be as high as 50%. Thus, audiologic evaluation is indicated.

DNA-based testing of the known causative genes, which can be performed via next-generation sequencing, can be considered for confirmation of diagnosis.[18] Unless a known mutation is present in a family, negative (ie, normal) test findings do not rule out a diagnosis of Noonan syndrome.

Contributor Information and Disclosures

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Elaine H Zackai, MD Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate-Craniofacial Association, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.


Jennifer Ibrahim, MD Chief, Genetics Division, St Joseph's Children's Hospital

Jennifer Ibrahim, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

  1. Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct. 126(4):746-59. [Medline]. [Full Text].

  2. Kratz CP, Rapisuwon S, Reed H, et al. Cancer in Noonan, Costello, cardiofaciocutaneous and LEOPARD syndromes. Am J Med Genet C Semin Med Genet. 2011 May 15. 157C(2):83-9. [Medline]. [Full Text].

  3. Jongmans MC, van der Burgt I, Hoogerbrugge PM, et al. Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. Eur J Hum Genet. 2011 Aug. 19(8):870-4. [Medline].

  4. Niemczyk J, Equit M, Borggrefe-Moussavian S, Curfs L, von Gontard A. Incontinence in persons with Noonan Syndrome. J Pediatr Urol. 2015 Jun 18. [Medline].

  5. Cessans C, Ehlinger V, Arnaud C, et al. Growth patterns of patients with Noonan syndrome: correlation with age and genotype. Eur J Endocrinol. 2016 May. 174 (5):641-50. [Medline].

  6. van Trier DC, van Nierop J, Draaisma JM, et al. External ear anomalies and hearing impairment in Noonan Syndrome. Int J Pediatr Otorhinolaryngol. 2015 Jun. 79 (6):874-8. [Medline].

  7. National Institutes of Health. Noonan-like/Multiple Giant Cell Lesion Syndrome. Genetic and Rare Diseases Information Center (GARD). Available at Accessed: Dec 1 2014.

  8. Allanson JE, Bohring A, Dörr HG, et al. The face of Noonan syndrome: Does phenotype predict genotype. Am J Med Genet A. 2010 Aug. 152A(8):1960-6. [Medline]. [Full Text].

  9. Miyamoto JJ, Yabunaka T, Moriyama K. Cervical characteristics of Noonan syndrome. Eur J Orthod. 2013 May 9. [Medline].

  10. Tartaglia M, Kalidas K, Shaw A, et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet. 2002 Jun. 70(6):1555-63. [Medline].

  11. Tartaglia M, Pennacchio LA, Zhao C, et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet. 2007 Jan. 39(1):75-9. [Medline].

  12. Pandit B, Sarkozy A, Pennacchio LA, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007 Aug. 39(8):1007-12. [Medline].

  13. Schubbert S, Zenker M, Rowe SL, et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet. 2006 Mar. 38(3):331-6. [Medline].

  14. Carta C, Pantaleoni F, Bocchinfuso G, et al. Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Am J Hum Genet. 2006 Jul. 79(1):129-35. [Medline].

  15. Pierpont EI, Pierpont ME, Mendelsohn NJ, Roberts AE, Tworog-Dube E, Seidenberg MS. Genotype differences in cognitive functioning in Noonan syndrome. Genes Brain Behav. 2009 Apr. 8(3):275-82. [Medline]. [Full Text].

  16. Lee BH, Kim JM, Jin HY, et al. Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. J Pediatr. 2011 Dec. 159(6):1029-35. [Medline].

  17. Roelofs RL, Janssen N, Wingbermuhle E, Kessels RP, Egger JI. Intellectual development in Noonan syndrome: a longitudinal study. Brain Behav. 2016 May 3. e00479. [Medline]. [Full Text].

  18. Lepri FR, Scavelli R, Digilio MC, et al. Diagnosis of Noonan syndrome and related disorders using target next generation sequencing. BMC Med Genet. 2014 Jan 23. 15:14. [Medline]. [Full Text].

  19. Sekhri N. Noonan Syndrome. RCPU Newsletter. Jan 2009. XX(2):[Full Text].

  20. Romano AA, Dana K, Bakker B, 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 Apr 28. [Medline].

  21. Binder G. Noonan syndrome, the Ras-MAPK signalling pathway and short stature. Horm Res. 2009 Apr. 71 Suppl 2:64-70. [Medline].

  22. Houweling AC, de Mooij YM, van der Burgt I, et al. Prenatal detection of Noonan syndrome by mutation analysis of the PTPN11 and the KRAS genes. Prenat Diagn. 2010 Mar. 30(3):284-6. [Medline].

  23. Allanson JE. Noonan syndrome. J Med Genet. 1987 Jan. DA - 19870320(1):9-13. [Medline].

  24. Allanson JE, Hall JG, Hughes HE, et al. Noonan syndrome: the changing phenotype. Am J Med Genet. 1985 Jul. 21(3):507-14. [Medline].

  25. Aoki Y, Niihori T, Narumi Y, Kure S, Matsubara Y. The RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders. Hum Mutat. 2008 Aug. 29(8):992-1006. [Medline].

  26. Bader-Meunier B, Tchernia G, Mielot F, et al. Occurrence of myeloproliferative disorder in patients with Noonan syndrome. J Pediatr. 1997 Jun. 130(6):885-9. [Medline].

  27. Bertelloni S, Baroncelli GI, Dati E, Ghione S, Baldinotti F, Toschi B, et al. IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene. Hormones (Athens). 2013 Jan. 12(1):86-92. [Medline].

  28. Ferrero GB, Baldassarre G, Delmonaco AG, Biamino E, Banaudi E, Carta C, et al. Clinical and molecular characterization of 40 patients with Noonan syndrome. Eur J Med Genet. 2008 Nov-Dec. 51(6):566-72. [Medline].

  29. Marino B, Digilio MC, Toscano A, et al. Congenital heart diseases in children with Noonan syndrome: An expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr. 1999 Dec. 135(6):703-6. [Medline].

  30. Noonan JA. Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease. Am J Dis Child. 1968 Oct. 116(4):373-80. [Medline].

  31. Noonan JA. Noonan syndrome revisited. J Pediatr. 1999 Dec. 135(6):667-8. [Medline].

  32. Noonan JA. Noonan syndrome. An update and review for the primary pediatrician. Clin Pediatr (Phila). 1994 Sep. 33(9):548-55. [Medline].

  33. Qiu WW, Yin SS, Stucker FJ. Audiologic manifestations of Noonan syndrome. Otolaryngol Head Neck Surg. 1998 Mar. 118(3 Pt 1):319-23. [Medline].

  34. Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013 Jan 26. 381(9863):333-42. [Medline].

  35. Sharland M, Burch M, McKenna WM, Paton MA. A clinical study of Noonan syndrome. Arch Dis Child. 1992 Feb. 67(2):178-83. [Medline].

  36. Sharland M, Morgan M, Smith G, et al. Genetic counseling in Noonan syndrome. Am J Med Genet. 1993 Feb 15. 45(4):437-40. [Medline].

  37. Singer ST, Hurst D, Addiego JE Jr. Bleeding disorders in Noonan syndrome: three case reports and review of the literature. J Pediatr Hematol Oncol. 1997 Mar-Apr. 19(2):130-4. [Medline].

  38. van der Burgt I, Thoonen G, Roosenboom N, et al. Patterns of cognitive functioning in school-aged children with Noonan syndrome associated with variability in phenotypic expression. J Pediatr. 1999 Dec. 135(6):707-13. [Medline].

  39. Zenker M. Genetic and pathogenetic aspects of Noonan syndrome and related disorders. Horm Res. 2009 Dec. 72 Suppl 2:57-63. [Medline].

Lymphedema of the feet in an infant is shown. The toes have the characteristic sausagelike appearance.
Generalized lymphedema is seen here in an infant. The loose skin folds around the neck will form a webbed neck later in life.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.