Annals of Pediatric Endocrinology and Metabolism

  • 제23권4호
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  • Pages.176-181
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  • 2018
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  • 2287-1012(pISSN)
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  • 2287-1292(eISSN)
대한소아내분비학회 (Korean Society of Pediatric Endocrinology)
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Growth hormone therapy in patients with Noonan syndrome

  • Seo, Go Hun (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
  • 투고 : 2018.10.24
  • 심사 : 2018.12.09
  • 발행 : 2018.12.30
⟨ 이전 논문 다음 논문 ⟩

초록

Noonan syndrome (NS) is an autosomal dominant disorder that involves multiple organ systems, with short stature as the most common presentation (>70%). Possible mechanisms of short stature in NS include growth hormone (GH) deficiency, neurosecretory dysfunction, and GH resistance. Accordingly, GH therapy has been carried out for NS patients over the last three decades, and multiple studies have reported acceleration of growth velocity (GV) and increase of height standard deviation score (SDS) in both prepubertal and pubertal NS patients upon GH therapy. One year of GH therapy resulted in almost doubling of GV compared with baseline; afterwards, the increase in GV gradually decreased in the following years, showing that the effect of GH therapy wanes over time. After four years of GH therapy, ~70% of NS patients reached normal height considering their age and sex. Early initiation, long duration of GH therapy, and higher height SDS at the onset of puberty were associated with improved final height, whereas gender, dosage of GH, and the clinical severity did not show significant association with final height. Studies have reported no significant adverse events of GH therapy regarding progression of hypertrophic cardiomyopathy, alteration of metabolism, and tumor development. Therefore, GH therapy is effective for improving height and GV of NS patients; nevertheless, concerns on possible malignancy remains, which necessitates continuous monitoring of NS patients receiving GH therapy.

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참고문헌

  1. Mendez HM, Opitz JM. Noonan syndrome: a review. Am J Med Genet 1985;21:493-506. https://doi.org/10.1002/ajmg.1320210312
  2. Digilio MC, Conti E, Sarkozy A, Mingarelli R, Dottorini T, Marino B, et al. Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. Am J Hum Genet 2002;71:389-94. https://doi.org/10.1086/341528
  3. 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. https://doi.org/10.1136/jmg.2007.050450
  4. 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. https://doi.org/10.1002/humu.20748
  5. Jorge AA, Malaquias AC, Arnhold IJ, Mendonca BB. 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.
  6. Lee BH, Kim JM, Jin HY, Kim GH, Choi JH, Yoo HW. Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. J Pediatr 2011;159:1029-35. https://doi.org/10.1016/j.jpeds.2011.05.024
  7. Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet 2013;381:333-42. https://doi.org/10.1016/S0140-6736(12)61023-X
  8. Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 2003;3:459-65. https://doi.org/10.1038/nrc1097
  9. Giehl K. Oncogenic Ras in tumour progression and metastasis. Biol Chem 2005;386:193-205.
  10. Ko JM, Kim JM, Kim GH, Yoo HW. PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome. J Hum Genet 2008;53:999-1006. https://doi.org/10.1007/s10038-008-0343-6
  11. Cordeddu V, Di Schiavi E, Pennacchio LA, 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. https://doi.org/10.1038/ng.425
  12. 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;148:220-7. https://doi.org/10.1007/BF00441408
  13. Shaw AC, Kalidas K, Crosby AH, Jeffery S, Patton MA. The natural history of Noonan syndrome: a long-term followup study. Arch Dis Child 2007;92:128-32.
  14. Binder G, Grathwol S, von Loeper K, Blumenstock G, Kaulitz R, Freiberg C, et al. Health and quality of life in adults with Noonan syndrome. J Pediatr 2012;161:501-5.e1. https://doi.org/10.1016/j.jpeds.2012.02.043
  15. Romano AA, Blethen SL, Dana K, Noto RA. Growth hormone treatment in Noonan syndrome: the National Cooperative Growth Study experience. J Pediatr 1996;128(5 Pt 2):S18-21. https://doi.org/10.1016/S0022-3476(96)70005-7
  16. Tamburrino F, Gibertoni D, Rossi C, Scarano E, Perri A, Montanari F, et al. Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: patterns of growth, puberty and final height data. Am J Med Genet A 2015;167A:2786-94.
  17. Noordam C, van der Burgt I, Sweep CG, Delemarre-van de Waal HA, Sengers RC, Otten BJ. Growth hormone (GH) secretion in children with Noonan syndrome: frequently abnormal without consequences for growth or response to GH treatment. Clin Endocrinol (Oxf) 2001;54:53-9. https://doi.org/10.1046/j.1365-2265.2001.01188.x
  18. Ferreira LV, Souza SA, Arnhold IJ, Mendonca BB, Jorge AA. 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. https://doi.org/10.1210/jc.2004-2559
  19. Limal JM, Parfait B, Cabrol S, Bonnet D, Leheup B, Lyonnet S, et al. Noonan syndrome: relationships between genotype, growth, and growth factors. J Clin Endocrinol Metab 2006;91:300-6. https://doi.org/10.1210/jc.2005-0983
  20. Cotterill AM, McKenna WJ, Brady AF, Sharland M, Elsawi M, Yamada M, et al. The short-term effects of growth hormone therapy on height velocity and cardiac ventricular wall thickness in children with Noonan's syndrome. J Clin Endocrinol Metab 1996;81:2291-7.
  21. Choi JH, Lee BH, Jung CW, Kim YM, Jin HY, Kim JM, et al. Response to growth hormone therapy in children with Noonan syndrome: correlation with or without PTPN11 gene mutation. Horm Res Paediatr 2012;77:388-93. https://doi.org/10.1159/000339677
  22. MacFarlane CE, Brown DC, Johnston LB, Patton MA, Dunger DB, Savage MO, et al. Growth hormone therapy and growth in children with Noonan's syndrome: results of 3 years' follow-up. J Clin Endocrinol Metab 2001;86:1953-6.
  23. Jeong I, Kang E, Cho JH, Kim GH, Lee BH, Choi JH, et al. Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome. Ann Pediatr Endocrinol Metab 2016;21:26-30. https://doi.org/10.6065/apem.2016.21.1.26
  24. Lee PA, Ross J, Germak JA, Gut R. Effect of 4 years of growth hormone therapy in children with Noonan syndrome in the American Norditropin Studies: Web-Enabled Research (ANSWER) $Program^{(R)}$ registry. Int J Pediatr Endocrinol 2012;2012:15. https://doi.org/10.1186/1687-9856-2012-15
  25. Noordam C, Peer PG, Francois I, De Schepper J, van den Burgt I, Otten BJ. Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, nonreceptor-type 11. Eur J Endocrinol 2008;159:203-8. https://doi.org/10.1530/EJE-08-0413
  26. Romano AA, Dana K, Bakker B, Davis DA, Hunold JJ, Jacobs J, 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;94:2338-44. https://doi.org/10.1210/jc.2008-2094
  27. Osio D, Dahlgren J, Wikland KA, Westphal O. Improved final height with long-term growth hormone treatment in Noonan syndrome. Acta Paediatr 2005;94:1232-7. https://doi.org/10.1111/j.1651-2227.2005.tb02081.x
  28. Raaijmakers R, Noordam C, Karagiannis G, Gregory JW, Hertel NT, Sipila I, et al. Response to growth hormone treatment and final height in Noonan syndrome in a large cohort of patients in the KIGS database. J Pediatr Endocrinol Metab 2008;21:267-73.
  29. Noordam K, van der Burgt I, Brunner HG, Otten BJ. The relationship between clinical severity of Noonan's syndrome and growth, growth hormone (GH) secretion and response to GH treatment. J Pediatr Endocrinol Metab 2002;15:175-80.
  30. Binder G, Neuer K, Ranke MB, Wittekindt NE. PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. J Clin Endocrinol Metab 2005;90:5377-81. https://doi.org/10.1210/jc.2005-0995
  31. Noordam C, Draaisma JM, van den Nieuwenhof J, van der Burgt I, Otten BJ, Daniels O. Effects of growth hormone treatment on left ventricular dimensions in children with Noonan's syndrome. Horm Res 2001;56:110-3.
  32. Jongmans MC, van der Burgt I, Hoogerbrugge PM, Noordam K, Yntema HG, Nillesen WM, et al. Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. Eur J Hum Genet 2011;19:870-4. https://doi.org/10.1038/ejhg.2011.37
  33. McWilliams GD, SantaCruz K, Hart B, Clericuzio C. Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy. Am J Med Genet A 2016;170A:195-201.

피인용 문헌

  1. A case of Noonan syndrome diagnosed using the facial recognition software (FACE2GENE) vol.16, pp.2, 2018, https://doi.org/10.5734/jgm.2019.16.2.81
  2. Long-term efficacy and safety of two doses of Norditropin® (somatropin) in Noonan syndrome: a 4-year randomized, double-blind, multicenter trial in Japanese patients vol.67, pp.8, 2018, https://doi.org/10.1507/endocrj.ej19-0371
  3. Short stature and growth hormone deficiency in a subset of patients with Potocki–Lupski syndrome: Expanding the phenotype of PTLS vol.182, pp.9, 2020, https://doi.org/10.1002/ajmg.a.61741
  4. Effect of Growth Hormone Therapy in Patients with Noonan Syndrome: A Retrospective Study vol.18, pp.4, 2020, https://doi.org/10.5812/ijem.107292
  5. Lack of Catch-Up Growth with Growth Hormone Treatment in a Child Born Small for Gestational Age Leading to a Diagnosis of Noonan Syndrome with a Pathogenic PTPN11 Variant vol.2021, pp.None, 2018, https://doi.org/10.1155/2021/5571524