Abstract：
Noonan syndrome (NS) is a relatively common developmental disorder characterised by the association of craniofacial abnormalities, congenital heart defects, short stature and skeletal abnormalities, variable developmental delay/learning disability, and predisposition to certain cancers. NS is caused by germline mutations in genes encoding components or regulators of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. Although abnormalities in the hypothalamic-pituitary-gonadal axis have long been reported in NS patients, there is only scarce published data on this subject. Puberty is usually delayed of about two years for both boys and girls with NS. However, in the majority of patients, it starts spontaneously suggesting a normal hypothalamic - pituitary input. The lower fat mass usually observed in NS patients may influence the timing of puberty. Although there is almost no reliable data on this issue, it is usually considered that fertility is not affected in NS females. In contrast, primary testicular insufficiency, predominant on Sertoli cell function, is reported in NS males. However, the exact frequency of infertility in adult males is unknown. More generally, although the features of NS are well described during childhood, little is known about the progression of the disease in adulthood. Prospective long-term follow-up studies are required to further investigate gonadal function and fertility in NS adults and to clarify the long-term follow-up of these patients.
摘要：
Noonan综合征（NS）是一种相对常见的发育障碍，其特征是颅面异常。先天性心脏缺陷,身材矮小和骨骼异常，可变发育延迟/学习障碍，和某些癌症的易感性。NS是由RAS/丝裂原激活的蛋白激酶（MAPK）信号通路的编码成分或调节因子的基因中的种系突变引起的。尽管在NS患者中一直有下丘脑-垂体-性腺轴异常的报道，关于这个问题的公开数据很少。对于患有NS的男孩和女孩，青春期通常会延迟约两年。然而,在大多数患者中，它开始自发地提示正常的下丘脑-垂体输入。通常在NS患者中观察到的较低的脂肪量可能会影响青春期的时机。尽管在这个问题上几乎没有可靠的数据，通常认为NS女性的生育能力不受影响。相比之下,原发性睾丸功能不全,以支持细胞功能为主，据报道，NS男性。然而,成年男性不育的确切频率尚不清楚。更一般地说,尽管NS的特征在童年时期得到了很好的描述，对这种疾病在成年后的进展知之甚少。需要进行前瞻性长期随访研究，以进一步调查NS成人的性腺功能和生育能力，并阐明这些患者的长期随访。
