Abstract
Noonan syndrome is an autosomal dominant disease that manifests a wide variety of clinical characteristics. The syndrome is also associated with some cardiac defects. Half of all Noonan syndrome cases are caused by mutations in the PTPN11 gene, but only limited data are available regarding aortic involvement in these cases. No reports exist regarding PTPN11 mutations in association with both aortic dilation and hypertrophic cardiomyopathy. We describe an 8-year-old girl who had Noonan syndrome involving a PTPN11 mutation, hypertrophic cardiomyopathy, main pulmonary artery dilation, and aortic root dilation. To our knowledge, this is the first case in which all three of these cardiovascular features have been observed in a single patient with Noonan syndrome.
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References
Allanson JE (1987) Noonan syndrome. J Med Genet 24:9–13
Bertola DR, Pereira AC, Albano LM, De Oliveira PS, Kim CA, Krieger JE (2006) PTPN11 gene analysis in 74 Brazilian patients with Noonan syndrome or Noonan-like phenotype. Genet Test 10:186–191
Ishizawa A, Oho S, Dodo H, Katori T, Homma SI (1996) Cardiovascular abnormalities in Noonan syndrome: the clinical findings and treatments. Acta Paediatr Jpn 38:84–90
Ko JM, Kim JM, Kim GH, Yoo HW (2008) PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome. J Hum Genet 53:999–1006
Musante L, Kehl HG, Majewski F, Meinecke P, Schweiger S, Gillessen-Kaesbach G, Wieczorek D, Hinkel GK, Tinschert S, Hoeltzenbein M, Ropers HH, Kalscheuer VM (2003) Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. Eur J Hum Genet 11:201–206
Narumi Y, Aoki Y, Niihori T, Sakurai M, Cave H, Verloes A, Nishio K, Ohashi H, Kurosawa K, Okamoto N, Kawame H, Mizuno S, Kondoh T, Addor MC, Coeslier-Dieux A, Vincent-Delorme C, Tabayashi K, Aoki M, Kobayashi T, Guliyeva A, Kure S, Matsubara Y (2008) Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome. J Hum Genet 53:834–841
Noonan JA (1968) Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease. Am J Dis Child 116:373–380
Power PD, Lewin MB, Hannibal MC, Glass IA (2006) Aortic root dilatation is a rare complication of Noonan syndrome. Pediatr Cardiol 27:478–880
Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, Kamisago M, Momma K, Katayama H, Nakagawa M, Fujiwara Y, Matsushima M, Mizuno K, Tokuyama M, Hirota H, Muneuchi J, Higashinakagawa T, Matsuoka R (2007) Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet 39:1013–1017
Schubbert S, Zenker M, Rowe SL, Boll S, Klein C, Bollag G, van der Burgt I, Musante L, Kalscheuer V, Wehner LE, Nguyen H, West B, Zhang KY, Sistermans E, Rauch A, Niemeyer CM, Shannon K, Kratz CP (2006) Germline KRAS mutations cause Noonan syndrome. Nat Genet 38:331–336
Sznajer Y, Keren B, Baumann C, Pereira S, Alberti C, Elion J, Cave H, Verloes A (2007) The spectrum of cardiac anomalies in Noonan syndrome as a result of mutations in the PTPN11 gene. Pediatrics 119:e1325–e1331
Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD (2002) PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype–phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet 70:1555–1563
Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, Zampino G, Burgt I, Palleschi A, Petrucci TC, Sorcini M, Schoch C, Foa R, Emanuel PD, Gelb BD (2006) Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am J Hum Genet 78:279–290
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 (2001) Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29:465–468
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 (2007) Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet 39:75–79
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Jefferies, J.L., Belmont, J.W., Pignatelli, R. et al. PTPN11 Mutation Associated with Aortic Dilation and Hypertrophic Cardiomyopathy in a Pediatric Patient with Noonan Syndrome. Pediatr Cardiol 31, 114–116 (2010). https://doi.org/10.1007/s00246-009-9537-8
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DOI: https://doi.org/10.1007/s00246-009-9537-8