Department of Biomedical Sciences and Human Oncology, Pediatric Unit, University of Bari "A. Moro", Bari, Italy.
National Research Council-Institute of Sciences of Food Production (CNR-ISPA), Bari, Italy.
Front Endocrinol (Lausanne). 2021 Dec 22;12:761171. doi: 10.3389/fendo.2021.761171. eCollection 2021.
Growth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children.
Retrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement.
ANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from -3.10 ± 0.84 to -2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH.
rhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of gene and in the less common genotypes.
生长障碍是努南综合征（Noonan syndrome，NS）的常见表现。已有研究表明，重组人生长激素（recombinant human GH，rhGH）治疗可促进生长和成年身高（adult height，AH）。本研究旨在评估 NS 患儿的生长轨迹和 rhGH 治疗效果。
这是一项回顾性、多中心、队列研究，纳入了基因诊断为 NS 的患者。共纳入 228 例 NS 患儿，其中 154 例存在 基因突变，94 例达到 AH。在 2、5、10 岁，青春期开始时和 AH 时采集人体测量学数据。68 例 GH 缺乏（growth hormone deficiency，GHD）的 NS 患儿接受 rhGH 治疗，平均剂量为 0.24 mg/kg/周，直至达到 AH。
方差分析显示，在不同关键年龄（）时，出生时的身长和身高标准差评分（height standard deviation scores，HSDS）存在显著差异，而在 2、5、10 岁，青春期开始时和 AH 时的 HSDS 测量值无显著差异。在 rhGH 治疗期间，HSDS 从 -3.10 ± 0.84 增加到 -2.31 ± 0.99，身高增加了 0.79 ± 0.74，未治疗的 NS 与治疗后的 NS 在 AH 时无显著差异。
对于儿童特发性 GH 缺乏症，采用标准剂量的 rhGH 治疗可有效改善 GHD 的 NS 患儿的生长和 AH。需要进一步研究评估不同 基因突变和较少见基因型对 rhGH 治疗的基因型特异性反应。
