Department of Pediatric Endocrinology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
Endocr Pract. 2023 Nov;29(11):902-911. doi: 10.1016/j.eprac.2023.08.013. Epub 2023 Aug 30.
Bioinactive growth hormone (BGH) is a structurally abnormal, biologically inactive, but immunoreactive form of growth hormone encoded by pathogenic growth hormone 1 gene variants. The underlying cause of the defective physiology is decreased BGH binding affinity to both growth hormone binding proteins and growth hormone receptors (GHRs). GHR cannot dimerize when it is in a quiescent state because BGH cannot activate it. Nondimerized GHR is unable to activate intracytoplasmic signaling pathway molecules such as Janus kinase 2 and signal transducer and activator of transcription, which initiate insulin-like growth factor-1 (IGF-1) transcription. IGF-1 cannot therefore be synthesized and IGF-1 levels in the circulation decrease. In contrast to children with growth hormone insensitivity, children with short stature due to BGH, known as Kowarski syndrome, exhibit an outstanding linear growth response to recombinant growth hormone therapy. For a number of reasons, differential diagnosis presents some difficulties. Similar diseases caused by genetic abnormalities that cause short stature range in severity from minor to severe clinical spectrum. Furthermore, some patients with Kowarski syndrome have previously been diagnosed with familial short stature, constitutional delayed puberty, and idiopathic short stature. This paper aims to review the particular clinical and laboratory findings of BGH.
This study collected clinical and laboratory data from KS cases reported in the literature.
This review reports that KS cases have lower SDSs for height and IGF-1 compared to growth hormone deficiency.
The diversity of genetic defects underlying Kowarski syndrome (KS) will provide new insights into growth hormone insensitivity. As the availability of genetic analysis, including functional investigations expands, researchers will identify new underlying genetic pathways.
生物活性生长激素（BGH）是一种结构异常、生物活性丧失但具有免疫反应性的生长激素形式，由致病生长激素 1 基因变异体编码。其潜在的生理缺陷是 BGH 与生长激素结合蛋白和生长激素受体（GHR）的结合亲和力降低。当 GHR 处于静止状态时，由于 BGH 无法激活它，因此无法二聚化。未二聚化的 GHR 无法激活细胞内信号通路分子，如 Janus 激酶 2 和信号转导和转录激活因子，这些分子启动胰岛素样生长因子-1（IGF-1）的转录。因此，无法合成 IGF-1，循环中的 IGF-1 水平下降。与生长激素不敏感的儿童不同，由于 BGH 导致身材矮小的儿童，即 Kowarski 综合征，对重组生长激素治疗表现出出色的线性生长反应。由于多种原因，鉴别诊断存在一些困难。由导致身材矮小的遗传异常引起的类似疾病，其严重程度从轻度到重度临床谱不等。此外，一些 Kowarski 综合征患者以前被诊断为家族性身材矮小、体质性青春期延迟和特发性身材矮小。本文旨在回顾 BGH 的特定临床和实验室发现。
本研究从文献中报道的 KS 病例中收集了临床和实验室数据。
本综述报告称，KS 病例的身高 SDS 和 IGF-1 均低于生长激素缺乏症。
Kowarski 综合征（KS）的遗传缺陷多样性将为生长激素不敏感提供新的见解。随着包括功能研究在内的遗传分析可用性的增加，研究人员将确定新的潜在遗传途径。
