努南综合征 (NS) 和毛发生长初期毛发松散的努南样综合征 (NS/LAH) 是由参与大鼠肉瘤/丝裂原激活蛋白激酶 (RAS/MAPK) 途径的基因种系突变引起的神经发育综合征。这项回顾性研究的目的是描述 NS 和 NS/LAH 的常见和罕见表现。我们收集并分析了 25 名 NS 和 NS/LAH 患者的临床和遗传数据。患者的中位年龄为 6.3 岁（范围，1 -13岁），男女比例为18：7。总共有 19 名患者患有由 PTPN11 突变引起的 NS。在6名患者中发现了另一种致病基因，包括2名SHOC2突变患者、1名KRAS突变患者、1名LZTR1突变患者、1名BRAF突变患者和1名PPP1CB突变患者。 100% 的患者均被检测出身材矮小。本研究概述了 NS 的临床特征，包括独特的面部特征、身材矮小、先天性心脏缺陷和其他表现。值得注意的是，在两名 SHOC2 阳性患者中发现了系统性红斑狼疮 (SLE)。一名患者患有后尿道瓣膜，这在 NS 患者中非常罕见。我们的研究发现了一些以前与 NS 关系不大的临床特征，包括 SLE。我们的结论是，SHOC2 相关的 NS 与特别高的 SLE 风险相关，这可能对生活质量产生重大影响，而后尿道瓣膜是一种新的表型。这些发现可能有助于增强对 NS.2024 转化儿科临床谱的理解。版权所有。

Noonan syndrome (NS) and Noonan-like syndrome with loose anagen hair (NS/LAH) are neurodevelopmental syndromes resulting from germline mutations in genes that participate in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway. The aim of this retrospective study was to describe common and rare manifestations of NS and NS/LAH.We collected and analyzed clinical and genetic data from 25 patients with NS and NS/LAH.The patients' median age was 6.3 years (range, 1-13 years), and the male-to-female ratio was 18:7. In total, 19 patients had NS caused by a mutation in PTPN11. Another causative gene was found in six patients, including two patients with a SHOC2 mutation, one patient with a KRAS mutation, one patient with an LZTR1 mutation, one patient with a BRAF mutation, and one patient with a PPP1CB mutation. Short stature was detected in 100% of the patients. This study provides an overview of the clinical features of NS, including unique facial features, short stature, congenital heart defects, and other manifestations. Notably, systemic lupus erythematosus (SLE) was found in two SHOC2-positive patients. One patient had a posterior urethral valve, which is very rare in NS patients.Our study identified several clinical features that were previously poorly related to NS, including SLE. We concluded that SHOC2-related NS is associated with a particularly high risk of SLE, which may have a significant impact on quality of life, and a posterior urethral valve is a novel phenotype. These findings could be helpful in enhancing the understanding of the clinical spectrum of NS.2024 Translational Pediatrics. All rights reserved.