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Table of Contents
Vol. 72, Suppl. 2, 2009
Issue release date: December 2009
Horm Res 2009;72(suppl 2):3–7
(DOI:10.1159/000243772)

Noonan Syndrome: Introduction and Basic Clinical Features

Rohrer T.
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Abstract

Noonan syndrome (NS) is a fairly common (1 per 1,000–2,500 live births) autosomal dominantly inherited disorder and the most common syndromal cause of congenital heart disease after Down’s syndrome. The clinical features vary with age, but typical signs of NS include characteristic facial features with hypertelorism, down-slanting palpebral fissures, low-set posteriorly rotated ears, chest and spinal deformities, short stature, specific heart defects, learning disabilities and mild mental retardation. This article gives a brief introduction to NS and its basic clinical features using the established and generally accepted NS scoring system based on family history and facial, cardiac, growth, chest wall and other criteria. Aspects discussed include the definition, epidemiology, etiology, diagnosis and genetics of NS, as well as growth, skeletal and gonadal anomalies, pubertal development, ophthalmic and cutaneous abnormalities and the incidence of cancer in patients with NS.



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References

  1. Allanson JE: Noonan syndrome. J Med Genet 1987;24:9–13.
  2. Sharland M, Burch M, McKenna WM, Paton MA: A clinical study of Noonan syndrome. Arch Dis Child 1992;67:178–183.
  3. Allanson JE, Hall JG, Hughes HE, Preus M, Witt RD: Noonan syndrome: the changing phenotype. Am J Med Genet 1985;21:507–514.
  4. Kobylinski O: Ueber eine flughautähnliche Ausbreitung am Halse. Arch Anthropol 1883;14:342–348.
  5. Ullrich O: Über typische Kombinationsbilder multipler Abartungen. Z Kinderheilkd 1930;49:271–276.

    External Resources

  6. Noonan JA, Ehmke D: Associated noncardiac malformations in children with congenital heart disease. J Pediatr 1963;63:468–470.

    External Resources

  7. Noonan JA: Hypertelorism with Turner phenotype: a new syndrome with associated congenital heart disease. Am J Dis Child 1968;116:373–380.
  8. 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;53:187–191.
  9. Tartaglia M, Gelb BD: Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet 2005;6:45–68.
  10. Jamieson CR, van der Burgt I, Brady AF, van Reen M, Elsawi MM, Hol F, Jeffery S, Patton MA, Mariman E: Mapping a gene for Noonan syndrome to the long arm of chromosome 12. Nat Genet 1994;8:357–360.
  11. Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD: Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 2001;29:465–468.
  12. 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;29:992–1006.
  13. Roberts A, Allanson J, Jadico SK, Kavamura MI, Noonan J, Opitz JM, Young T, Neri G: The cardiofaciocutaneous syndrome. J Med Genet 2006;43:833–842.
  14. Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, Li L, Yassin Y, Tamburino AM, Neel BG, Kucherlapati RS: Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet 2007;39:70–74.
  15. Tartaglia M, Pennacchio LA, Zhao C, Yadav KK, Fodale V, Sarkozy A, Pandit B, Oishi K, Martinelli S, Schackwitz W, Ustaszewska A, Martin J, Bristow J, Carta C, Lepri F, Neri C, Vasta I, Gibson K, Curry CJ, Siguero JP, Digilio MC, Zampino G, Dallapiccola B, Bar-Sagi D, Gelb BD: Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet 2007;39:75–79.
  16. Zenker M, Horn D, Wieczorek D, Allanson J, Pauli S, van der Burgt I, Doerr HG, Gaspar H, Hofbeck M, Gillessen-Kaesbach G, Koch A, Meinecke P, Mundlos S, Nowka A, Rauch A, Reif S, von Schnakenburg C, Seidel H, Wehner LE, Zweier C, Bauhuber S, Matejas V, Kratz CP, Thomas C, Kutsche K: SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. J Med Genet 2007;44:651–656.
  17. Zenker M, Lehmann K, Schulz AL, Barth H, Hansmann D, Koenig R, Korinthenberg R, Kreiss-Nachtsheim M, Meinecke P, Morlot S, Mundlos S, Quante AS, Raskin S, Schnabel D, Wehner LE, Kratz CP, Horn D, Kutsche K: Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. J Med Genet 2007;44:131–135.
  18. van der Burgt I: Noonan syndrome. Orphanet J Rare Dis 2007;2:4.
  19. Allanson JE: Time and natural history: the changing face. J Craniofac Genet Dev Biol 1989;9:21–28.
  20. Sznajer Y, Keren B, Baumann C, Pereira S, Alberti C, Elion J, Cave H, Verloes A: The spectrum of cardiac anomalies in Noonan syndrome as a result of mutations in the PTPN11 gene. Pediatrics 2007;119:e1325–e1331.
  21. Jongmans M, Sistermans EA, Rikken A, Nillesen WM, Tamminga R, Patton M, Maier EM, Tartaglia M, Noordam K, van der Burgt I: Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature. Am J Med Genet A 2005;134A:165–170.
  22. 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;167:1363–1367.
  23. Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A, Bos JM, Ommen SR, Esposito G, Lepri F, Faul C, Mundel P, Lopez Siguero JP, Tenconi R, Selicorni A, Rossi C, Mazzanti L, Torrente I, Marino B, Digilio MC, Zampino G, Ackerman MJ, Dallapiccola B, Tartaglia M, Gelb BD: Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet 2007;39:1007–1012.
  24. 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;148:220–227.
  25. Limal JM, Parfait B, Cabrol S, Bonnet D, Leheup B, Lyonnet S, Vidaud M, Le BY: Noonan syndrome: relationships between genotype, growth, and growth factors. J Clin Endocrinol Metab 2006;91:300–306.
  26. 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;92:128–132.
  27. Neumann TE, Allanson J, Kavamura I, Kerr B, Neri G, Noonan J, Cordeddu V, Gibson K, Tzschach A, Kruger G, Hoeltzenbein M, Goecke TO, Kehl HG, Albrecht B, Luczak K, Sasiadek MM, Musante L, Laurie R, Peters H, Tartaglia M, Zenker M, Kalscheuer V: Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome. Eur J Hum Genet 2009;17:420–425.
  28. Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A: Genotype-phenotype correlations in Noonan syndrome. J Pediatr 2004;144:368–374.
  29. Kratz CP, Niemeyer CM, Castleberry RP, Cetin M, Bergstrasser E, Emanuel PD, Hasle H, Kardos G, Klein C, Kojima S, Stary J, Trebo M, Zecca M, Gelb BD, Tartaglia M, Loh ML: The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. Blood 2005;106:2183–2185.
  30. Lee NB, Kelly L, Sharland M: Ocular manifestations of Noonan syndrome. Eye 1992;6:328–334.
  31. Reynolds DJ, Rubin SE, Fox J, Kodsi SR: Ocular manifestations of Noonan syndrome in the pediatric patient. J AAPOS 2004;8:282–283.
  32. Piovesan EJ, Young Blood MR, Kowacs PA, Mulinari RA, Werneck LC, Sandrini R: Prevalence of migraine in Noonan syndrome. Cephalalgia 2007;27:330–335.
  33. Pierini DO, Pierini AM: Keratosis pilaris atrophicans faciei (ulerythema ophryogenes): a cutaneous marker in the Noonan syndrome. Br J Dermatol 1979;100:409–416.
  34. Levaillant JM, Gerard-Blanluet M, Holder-Espinasse M, Valat-Rigot AS, Devisme L, Cave H, Manouvrier-Hanu S: Prenatal phenotypic overlap of Costello syndrome and severe Noonan syndrome by tri-dimensional ultrasonography. Prenat Diagn 2006;26:340–344.
  35. Zenker M, Voss E, Reis A: Mild variable Noonan syndrome in a family with a novel PTPN11 mutation. Eur J Med Genet 2007;50:43–47.
  36. Verhoeven W, Wingbermuhle E, Egger J, van der Burgt I, Tuinier S: Noonan syndrome: psychological and psychiatric aspects. Am J Med Genet A 2008;146A:191–196.
  37. van der Burgt I, Thoonen G, Roosenboom N, Assman-Hulsmans C, Gabreels F, Otten B, Brunner HG: Patterns of cognitive functioning in school-aged children with Noonan syndrome associated with variability in phenotypic expression. J Pediatr 1999;135:707–713.


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