Peng Ji, Huang Ting, Wang Qiulan, Liu Bijing, Qin Luzhen, Yao Yuanyuan
Department of Children's Health Care, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, China.
Transl Pediatr. 2025 Aug 31;14(8):2057-2065. doi: 10.21037/tp-2025-422. Epub 2025 Aug 25.
Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by significant clinical heterogeneity, including distinctive facial features, short stature, developmental delay, congenital heart defects, and thoracic deformities. In some patients, especially in the early stages, the clinical manifestations are atypical and may solely include growth retardation or short stature, leading to misdiagnosis as idiopathic short stature or growth hormone (GH) deficiency and thereby delaying timely intervention.
In this report, a female child is described who exhibited slow weight and height gain since birth. At 18 months, physical examination revealed that her height was below the 3rd percentile, with bone age delayed by 3 months. No typical NS facial features or congenital heart defects were observed. GH stimulation testing indicated partial GH deficiency, and the insulin-like growth factor 1 (IGF-1) level was below normal; thus, a preliminary diagnosis of short stature due to GH insufficiency was made, and nutritional intervention was recommended. However, follow-up revealed a persistent slow growth velocity and progressive bone age delay. At 6 years and 1 month of age, whole-exome sequencing identified a heterozygous c.923A>G (p.Asn308Ser) variant in the gene, confirming the diagnosis of NS. Recombinant human growth hormone (rhGH) therapy was subsequently initiated. After rhGH intervention, the patient's annual height velocity increased by 2.4 to 3.2 times compared to pretreatment, which was accompanied by synchronous progression of bone age.
This case highlights the importance of early genetic testing in patients with persistent growth retardation unresponsive to standard interventions. rhGH therapy has been shown to be safe and effective in patients with NS and short stature, significantly promoting height gain and bone age development, and should be considered for broader clinical application.
努南综合征（NS）是一种常染色体显性遗传病，具有显著的临床异质性，包括独特的面部特征、身材矮小、发育迟缓、先天性心脏缺陷和胸廓畸形。在一些患者中，尤其是在疾病早期，临床表现不典型，可能仅包括生长发育迟缓或身材矮小，导致误诊为特发性矮小或生长激素（GH）缺乏，从而延误及时干预。
本报告描述了一名自出生以来体重和身高增长缓慢的女童。18个月时，体格检查发现其身高低于第3百分位数，骨龄延迟3个月。未观察到典型的努南综合征面部特征或先天性心脏缺陷。GH刺激试验表明部分GH缺乏，胰岛素样生长因子1（IGF-1）水平低于正常；因此，初步诊断为GH分泌不足导致的矮小症，并建议进行营养干预。然而，随访发现生长速度持续缓慢，骨龄延迟进展。在6岁1个月时，全外显子测序在该基因中鉴定出一个杂合的c.923A>G（p.Asn308Ser）变异，确诊为努南综合征。随后开始重组人生长激素（rhGH）治疗。rhGH干预后，患者的年身高增长速度比治疗前提高了2.4至3.2倍，同时骨龄同步进展。
该病例强调了对标准干预无反应的持续性生长发育迟缓患者进行早期基因检测的重要性。rhGH治疗已被证明对努南综合征和矮小症患者安全有效，可显著促进身高增长和骨龄发育，应考虑更广泛的临床应用。
