小结
定义
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] 常见凝血障碍、男性隐睾症及淋巴发育不良。[Figure caption and citation for the preceding image starts]: 男童，6 岁，患有 Noonan 综合征由 Judith E. Allanson 提供 [Citation ends].
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][3][4][5][6][7][8][9][10] 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][11][12]
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独特的疾病，而其他人则认为它仅可被归类为 Noonan 综合征。
病史和体格检查
关键诊断因素
- 阳性家族史
- 身材矮小
- 异常面容特征
- 隐睾症
- 心脏畸形
- 青春发育延迟
- 容易出血或出现淤伤
- 淋巴水肿
- 色素异常
- 眉毛和睫毛稀疏或缺如
- 脾肿大
其他诊断因素
- 产前发现异常
- 胸部畸形
- 发育迟缓/学习困难
- 骨骼异常
- 肌无力
- 肾畸形病史
危险因素
- NS 家族史
- 高父龄
诊断性检查
首要检查
- 心电图 (ECG）
- 超声心动图
需考虑的检查
- 全血细胞计数 (FBC）
- 凝血指标
- 分子遗传学检测
- 腹部超声
- 肾脏超声
治疗流程
所有患者
撰稿人
作者
David A. Stevenson, MD
Associate Professor
Department of Pediatrics
Division of Medical Genetics
Stanford University
Stanford
CA
利益声明
DAS has acted as a consultant for Lineagen, GLG, and Alexion, and has given expert testimony. He is on the medical advisory board for parents' support groups for Costello syndrome and CFC syndrome. DAS is an author of a reference cited in this topic. DAS has also been reimbursed by RASopathies Network for attending conferences.
鸣谢
Dr David A. Stevenson would like to gratefully acknowledge Dr Judith E. Allanson, the previous contributor to this topic. JEA is an author of a number of references cited in this topic.
同行评议者
Liliana N. Contreras, MD
Chief
Endocrine Research Department
Instituto de Investigaciones Médicas Alfredo Lanari
IDIM-CONICET
University of Buenos Aires
Argentina
利益声明
LNC declares that she has no competing interests.
Bruce Gelb, MD
Professor of Pediatrics
Mount Sinai School of Medicine
New York
NY
利益声明
BG received royalties from GeneDx, Correlegan, Preventative Genetics, Baylor College of Medicine, and Harvard Medical School/Partners for genetic testing of Noonan syndrome. BG is an author of a number of references cited in this topic.
Jacqueline Noonan, MD
Professor Emeriti
Department of Pediatrics
College of Medicine
University of Kentucky
Lexington
KY
利益声明
JN is on the Noonan Syndrome Advisory Board for Novo Nordisk and has received payment for speaking at a symposium. JN is an author of a number of references cited in this topic.
鉴别诊断
- 特纳综合征
- 豹皮综合征
- 心-面-皮肤综合征
更多 鉴别诊断指南
- 努南综合征：临床特征、诊断和治疗指南
更多 指南
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