Noonan 综合征

多达 80% 的病例中可见先天性心脏病损；因此，若怀疑为 Noonan 综合征，则应通过心电图进行心血管检查。[1]Jorge AA, Malaquias AC, Arnhold IJ, et al. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Horm Res. 2009;71(4):185-93.https://www.karger.com/Article/FullText/201106http://www.ncbi.nlm.nih.gov/pubmed/19258709?tool=bestpractice.com

最常见的心脏畸形包括肺动脉瓣发育不良和/或狭窄、肥厚型心肌病、间隔缺损及法洛四联症。[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[52]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%3Dihubhttp://www.ncbi.nlm.nih.gov/pubmed/8409059?tool=bestpractice.com[53]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[54]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

宽 QRS 复合波，伴左胸导联显著阴性 (62%)；心轴左偏，以及巨大 Q 波

多达 75% 的病例可见先天性心脏病损；因此，若怀疑为 Noonan 综合征，则应通过超声心动图进行心血管检查。[1]Jorge AA, Malaquias AC, Arnhold IJ, et al. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Horm Res. 2009;71(4):185-93.https://www.karger.com/Article/FullText/201106http://www.ncbi.nlm.nih.gov/pubmed/19258709?tool=bestpractice.com

最常见的心脏畸形包括肺动脉瓣发育不良和/或狭窄、肥厚型心肌病、间隔缺损及法洛四联症。[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[52]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%3Dihubhttp://www.ncbi.nlm.nih.gov/pubmed/8409059?tool=bestpractice.com[53]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[54]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

可能显示先天性心脏病

出血体质不太常见，若怀疑 Noonan 综合征，则应考虑进行凝血异常筛查，尤其是存在容易出血或出现淤伤时，或者计划手术时。

轻到中度的出血倾向并非罕见，[40]van der Burgt I. Noonan syndrome. Orphanet J Rare Dis. 2007 Jan 14;2:4.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781428/http://www.ncbi.nlm.nih.gov/pubmed/17222357?tool=bestpractice.com 但是文献中的患病率差异显著，[50]Briggs BJ, Dickerman JD. Bleeding disorders in Noonan syndrome. Pediatr Blood Cancer. 2012 Feb;58(2):167-72.http://www.ncbi.nlm.nih.gov/pubmed/22012616?tool=bestpractice.com 并且已有记录显示，存在多种类型的凝血功能障碍和出血体质。[49]Derbent M, Oncel Y, Tokel K, et al. Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. Am J Med Genet A. 2010 Nov;152A(11):2768-74.http://www.ncbi.nlm.nih.gov/pubmed/20954246?tool=bestpractice.com 据报道，约 3% 的病例曾出现严重出血。

血小板减少可能继发于血小板无效生成，伴有骨髓内巨核细胞的减少或缺失，或者源于增大的和/或骨髓增生异常的脾脏阻滞。[38]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.http://www.ncbi.nlm.nih.gov/pubmed/9149742?tool=bestpractice.com

贫血、血小板减少症

出血体质不太常见，若怀疑 Noonan 综合征，则应考虑进行凝血异常筛查，尤其是存在容易出血或出现淤伤时，或者计划手术时。[50]Briggs BJ, Dickerman JD. Bleeding disorders in Noonan syndrome. Pediatr Blood Cancer. 2012 Feb;58(2):167-72.http://www.ncbi.nlm.nih.gov/pubmed/22012616?tool=bestpractice.com

轻到中度的出血倾向并非罕见，[40]van der Burgt I. Noonan syndrome. Orphanet J Rare Dis. 2007 Jan 14;2:4.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781428/http://www.ncbi.nlm.nih.gov/pubmed/17222357?tool=bestpractice.com 但是文献中的患病率差异显著，[50]Briggs BJ, Dickerman JD. Bleeding disorders in Noonan syndrome. Pediatr Blood Cancer. 2012 Feb;58(2):167-72.http://www.ncbi.nlm.nih.gov/pubmed/22012616?tool=bestpractice.com 并且已有记录显示，存在多种类型的凝血功能障碍和出血体质。[49]Derbent M, Oncel Y, Tokel K, et al. Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. Am J Med Genet A. 2010 Nov;152A(11):2768-74.http://www.ncbi.nlm.nih.gov/pubmed/20954246?tool=bestpractice.com据报道，约 3% 的病例曾出现严重出血。

若存在凝血异常，则应将患者转诊至血液学专科医生以进行进一步的评估。[56]Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct;126(4):746-59.http://www.ncbi.nlm.nih.gov/pubmed/20876176?tool=bestpractice.com

凝血酶原时间、活化部分凝血活酶时间和出血时间可能延长

当诊断模棱两可时，或由于家庭原因（例如双亲诊断、确定复发风险或规划生育），则有必要进行该检测。

已有针对 Ras/MAPK 通路中所有已知可引起 Noonan 综合征的基因的临床诊断性检测。但是，部分 Noonan 综合征患者将不出现任何这些基因的突变。

部分实验室建议从 PTPN11 热点突变开始，进行分层筛查；而其他实验室则开发了使用定制芯片对所有已知基因编码区进行检测。

相关基因（例如 PTPN11、SOS1、RAF1、RIT1、RASA2、LZTR1、SHOC2、KRAS、NRAS、BRAF 和 MAP2K1）的特征性突变

若怀疑脾脏肿大，则应进行该检查。

脾肿大可能是脊髓发育不良的一个表现。[38]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.http://www.ncbi.nlm.nih.gov/pubmed/9149742?tool=bestpractice.com

可能显示脾肿大

若怀疑存在肾脏畸形（例如双重肾脏集合系统、远端输尿管狭窄、肾脏发育不良、单侧肾脏发育不良或单侧肾脏异位等畸形）则应进行肾脏超声检查；多达 10% 的病例可见肾脏畸形。[47]George CD, Patton MA, El Sawi M, et al. Abdominal ultrasound in Noonan syndrome: a study of 44 patients. Pediatr Radiol. 1993;23(4):316-8.http://www.ncbi.nlm.nih.gov/pubmed/8414765?tool=bestpractice.com

可能显示畸形