Síndrome de Noonan

Tratamento recomendado para TODOS os pacientes no grupo de pacientes selecionado

A abordagem cirúrgica é determinada pela preferência do cirurgião, geralmente por uma incisão inguinal ou escrotal.

Tratamento recomendado para TODOS os pacientes no grupo de pacientes selecionado

Esses defeitos incluem valva pulmonar estenótica e/ou displásica, cardiomiopatia hipertrófica, defeitos do septo e tetralogia de Fallot.[30]Shaw AC, Kalidas K, Crosby AH, et al. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007 Feb;92(2):128-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2083343 http://www.ncbi.nlm.nih.gov/pubmed/16990350?tool=bestpractice.com [55]Burch M, Sharland M, Shinebourne E, et al. Cardiologic abnormalities in Noonan syndrome: phenotypic diagnosis and echocardiographic assessment of 118 patients. J Am Coll Cardiol. 1993 Oct;22(4):1189-92. http://www.sciencedirect.com/science/article/pii/0735109793904365?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/8409059?tool=bestpractice.com [56]Ishizawa A, Oho S, Dodo H, et al. Cardiovascular abnormalities in Noonan syndrome: the clinical findings and treatments. Acta Paediatr Jpn. 1996 Feb;38(1):84-90. http://www.ncbi.nlm.nih.gov/pubmed/8992869?tool=bestpractice.com [57]Noonan JA, O'Connor W. Noonan syndrome: a clinical description emphasizing the cardiac findings. Acta Paediatr Jpn. 1996 Feb;38(1):76-83. http://www.ncbi.nlm.nih.gov/pubmed/8992867?tool=bestpractice.com

A avaliação cardiovascular abrangente no momento do diagnóstico é fundamental. O tratamento subsequente será orientado pela anomalia específica identificada.

A displasia e/ou estenose pulmonar valvar pode responder à valvoplastia por balão, mas pode exigir a substituição da valva.[56]Ishizawa A, Oho S, Dodo H, et al. Cardiovascular abnormalities in Noonan syndrome: the clinical findings and treatments. Acta Paediatr Jpn. 1996 Feb;38(1):84-90. http://www.ncbi.nlm.nih.gov/pubmed/8992869?tool=bestpractice.com A cardiomiopatia hipertrófica pode ser tratada com betabloqueadores ou bloqueio dos canais de cálcio, mas ocasionalmente requer miomectomia cirúrgica.[56]Ishizawa A, Oho S, Dodo H, et al. Cardiovascular abnormalities in Noonan syndrome: the clinical findings and treatments. Acta Paediatr Jpn. 1996 Feb;38(1):84-90. http://www.ncbi.nlm.nih.gov/pubmed/8992869?tool=bestpractice.com [57]Noonan JA, O'Connor W. Noonan syndrome: a clinical description emphasizing the cardiac findings. Acta Paediatr Jpn. 1996 Feb;38(1):76-83. http://www.ncbi.nlm.nih.gov/pubmed/8992867?tool=bestpractice.com

Os cuidados cardíacos devem continuar até a idade adulta, porque pode haver morbidade contínua e mortalidade associadas com os defeitos.[30]Shaw AC, Kalidas K, Crosby AH, et al. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007 Feb;92(2):128-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2083343 http://www.ncbi.nlm.nih.gov/pubmed/16990350?tool=bestpractice.com [56]Ishizawa A, Oho S, Dodo H, et al. Cardiovascular abnormalities in Noonan syndrome: the clinical findings and treatments. Acta Paediatr Jpn. 1996 Feb;38(1):84-90. http://www.ncbi.nlm.nih.gov/pubmed/8992869?tool=bestpractice.com

Tratamento recomendado para TODOS os pacientes no grupo de pacientes selecionado

Crianças com baixo crescimento documentado devem ser encaminhadas a um endocrinologista.

Foi relatado que o tratamento de crianças pequenas (5 anos de idade ou menos) com hormônio do crescimento (GH) apresenta maior otimização do crescimento, mas os riscos e benefícios de comorbidades, como cardiomiopatia hipertrófica e escoliose, devem ser considerados.[69]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 Jul;94(7):2338-44. http://www.ncbi.nlm.nih.gov/pubmed/19401366?tool=bestpractice.com

Estudos de tratamento com GH na síndrome de Noonan relatam ganhos de altura de 13 cm (5 polegadas) para homens.[66]Romano AA. Growth and Growth Hormone Treatment in Noonan Syndrome. Pediatr Endocrinol Rev. 2019 May;16(suppl 2):459-464. https://www.doi.org/10.17458/per.vol16.2019.r.growthhormonenoonan http://www.ncbi.nlm.nih.gov/pubmed/31115197?tool=bestpractice.com [67]Raaijmakers R, Noordam C, Karagiannis G, 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 Mar;21(3):267-73. http://www.ncbi.nlm.nih.gov/pubmed/18540254?tool=bestpractice.com [68]Osio D, Dahlgren J, Wikland KA, et al. Improved final height with long-term growth hormone treatment in Noonan syndrome. Acta Paediatr. 2005 Sep;94(9):1232-7. http://www.ncbi.nlm.nih.gov/pubmed/16203673?tool=bestpractice.com Um estudo demonstrou ganhos de altura quase comparáveis aos adultos de até 15 cm (6 polegadas) em pacientes tratados por uma média de 5 anos (idade média inicial de 11.6 anos).[69]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 Jul;94(7):2338-44. http://www.ncbi.nlm.nih.gov/pubmed/19401366?tool=bestpractice.com A duração do tratamento pré-puberal foi um importante contribuinte para a mudança na altura, sugerindo um potencial de crescimento mais alto com o início mais precoce do tratamento.[69]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 Jul;94(7):2338-44. http://www.ncbi.nlm.nih.gov/pubmed/19401366?tool=bestpractice.com [66]Romano AA. Growth and Growth Hormone Treatment in Noonan Syndrome. Pediatr Endocrinol Rev. 2019 May;16(suppl 2):459-464. https://www.doi.org/10.17458/per.vol16.2019.r.growthhormonenoonan http://www.ncbi.nlm.nih.gov/pubmed/31115197?tool=bestpractice.com O efeito do tratamento é monitorado pela resposta do crescimento e os níveis do fator de crescimento semelhante à insulina-1 (IGF-1). Variantes patogênicas no gene PTPN11 foram associadas à redução da resposta de crescimento ao GH na SN.[25]Binder G, Neuer K, Ranke MB, et al. PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. J Clin Endocrinol Metab. 2005 Sep;90(9):5377-81. https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2005-0995 http://www.ncbi.nlm.nih.gov/pubmed/15985475?tool=bestpractice.com [15]Limal JM, Parfait B, Cabrol S, et al. Noonan syndrome: relationships between genotype, growth, and growth factors. J Clin Endocrinol Metab. 2006 Jan;91(1):300-6. https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2005-0983 http://www.ncbi.nlm.nih.gov/pubmed/16263833?tool=bestpractice.com [70]Ferreira LV, Souza SA, Arnhold IJ, et al. PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. J Clin Endocrinol Metab. 2005 Sep;90(9):5156-60. https://academic.oup.com/jcem/article/90/9/5156/2838677 http://www.ncbi.nlm.nih.gov/pubmed/15956085?tool=bestpractice.com [71]Jeong I, Kang E, Cho JH, et al. Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome. Ann Pediatr Endocrinol Metab. 2016 Mar;21(1):26-30. https://www.doi.org/10.6065/apem.2016.21.1.26 http://www.ncbi.nlm.nih.gov/pubmed/27104176?tool=bestpractice.com No entanto, outros estudos relatam que a resposta à terapia com GH não difere significativamente de acordo com o genótipo.[72]Choi JH, Lee BH, Jung CW, et al. Response to growth hormone therapy in children with Noonan syndrome: correlation with or without PTPN11 gene mutation. Horm Res Paediatr. 2012;77(6):388-93. https://www.doi.org/10.1159/000339677 http://www.ncbi.nlm.nih.gov/pubmed/22777296?tool=bestpractice.com [73]Malaquias AC, Noronha RM, Souza TTO, et al. Impact of Growth Hormone Therapy on Adult Height in Patients with PTPN11 Mutations Related to Noonan Syndrome. Horm Res Paediatr. 2019;91(4):252-261. https://www.doi.org/10.1159/000500264 http://www.ncbi.nlm.nih.gov/pubmed/31132774?tool=bestpractice.com [74]Noordam C, Peer PG, Francois I, et al. Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11. Eur J Endocrinol. 2008 Sep;159(3):203-8. https://www.doi.org/10.1530/EJE-08-0413 http://www.ncbi.nlm.nih.gov/pubmed/18562489?tool=bestpractice.com [75]Seok EM, Park HK, Rho JG, et al. Effectiveness of growth hormone therapy in children with Noonan syndrome. Ann Pediatr Endocrinol Metab. 2020 Sep;25(3):182-186. https://www.doi.org/10.6065/apem.1938154.077 http://www.ncbi.nlm.nih.gov/pubmed/32871657?tool=bestpractice.com São necessários grandes estudos prospectivos para determinar se o genótipo influencia a resposta à terapia com GH.