相对常见的常染色体显性遗传病。
阅读更多特征性表型包括身材矮小、胸廓畸形、先天性心脏病及异常面容。
男孩通常出现隐睾症和明显的青春发育延迟。
由 Ras/丝裂原活化蛋白激酶 (mitogen-activated protein kinase, MAPK) 信号转导通路中多个基因的活化突变引起。最常涉及的基因是 PTPN11。
治疗将重点关注个体症状，男孩可能需要对未降睾丸行手术、优化心脏功能并针对身材矮小进行生长激素治疗。
大多数患者可以过正常的生活。50%-80% 的病例可能出现心脏疾病，预后在很大程度上取决于心脏疾病的类型和严重程度。
Noonan 综合征 (Noonan syndrome, NS) 是一种相对常见的常染色体显性遗传性疾病，主要表现为身材矮小、轻微面部异形、胸廓畸形、先天性心脏病和不同程度的发育延迟。[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
[Figure caption and citation for the preceding image starts]: 男孩，6 岁，患有 Noonan 综合征由 Judith E. Allanson 提供资料 [Citation ends]. 常见凝血障碍、男性隐睾症及淋巴发育不良。
阅读更多现在认为这种综合征主要是由 Ras/丝裂原活化蛋白激酶 (MAPK) 信号转导通路中基因的功能获得性（活化）突变引起。[2]Kratz CP, Niemeyer CM, Castleberry RP, et al. The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. Blood. 2005 Sep 15;106(6):2183-5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895140/http://www.ncbi.nlm.nih.gov/pubmed/15928039?tool=bestpractice.com[3]Roberts AE, Araki T, Swanson KD, et al. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet. 2007 Jan;39(1):70-4.http://www.ncbi.nlm.nih.gov/pubmed/17143285?tool=bestpractice.com[4]Tartaglia M, Pennacchio LA, Zhao C, et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet. 2007 Jan;39(1):75-9.http://www.ncbi.nlm.nih.gov/pubmed/17143282?tool=bestpractice.com[5]Pandit B, Sarkozy A, Pennacchio LA, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007 Aug;39(8):1007-12.http://www.ncbi.nlm.nih.gov/pubmed/17603483?tool=bestpractice.com[6]Razzaque MA, Nishizawa T, Komoike Y, et al. Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet. 2007 Aug;39(8):1013-7.http://www.ncbi.nlm.nih.gov/pubmed/17603482?tool=bestpractice.com[7]Schubbert S, Zenker M, Rowe SL, et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet. 2006 Mar;38(3):331-6.http://www.ncbi.nlm.nih.gov/pubmed/16474405?tool=bestpractice.com[8]Cirstea IC, Kutsche K, Dvorsky R, et al. A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet. 2010 Jan;42(1):27-9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118669/http://www.ncbi.nlm.nih.gov/pubmed/19966803?tool=bestpractice.com[9]Nyström AM, Ekvall S, Berglund E, et al. Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders. J Med Genet. 2008 Aug;45(8):500-6.http://www.ncbi.nlm.nih.gov/pubmed/18456719?tool=bestpractice.com[10]Sarkozy A, Carta C, Moretti S, et al. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat. 2009 Apr;30(4):695-702.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028130/http://www.ncbi.nlm.nih.gov/pubmed/19206169?tool=bestpractice.com 该病所涉及的基因包括： PTPN11、SOS1、RAF1、RIT1、RASA2、LZTR1、SOS2、CBL、KRAS、NRAS、BRAF、PPP1CB 和 MAP2K1。最常见的可识别的基因突变包括 PTPN11。[2]Kratz CP, Niemeyer CM, Castleberry RP, et al. The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. Blood. 2005 Sep 15;106(6):2183-5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895140/http://www.ncbi.nlm.nih.gov/pubmed/15928039?tool=bestpractice.com[11]Tartaglia M, Mehler EL, Goldberg R, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001 Dec;29(4):465-8.http://www.ncbi.nlm.nih.gov/pubmed/11704759?tool=bestpractice.com[12]Tartaglia M, Kalidas K, Shaw A, et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet. 2002 Jun;70(6):1555-63.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC379142/http://www.ncbi.nlm.nih.gov/pubmed/11992261?tool=bestpractice.com 目前大多数人认为 SHOC2 突变引起的 Noonan 综合征是一种具有不寻常特征（例如生长期毛发松动）的重叠性疾病，一些人认为它是一种不同的疾病，而其他人则认为它仅可被归类为 Noonan 综合征。
