Paparella Roberto, Bei Arianna, Bernabei Irene, Tarani Francesca, Niceta Marcello, Pucarelli Ida, Tarani Luigi
Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Department of Molecular Genetics and Functional Genomics, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Children (Basel). 2025 Jun 27;12(7):855. doi: 10.3390/children12070855.
Idiopathic short stature (ISS) represents one of the most frequent yet enigmatic conditions in pediatric endocrinology. Traditionally defined by auxological parameters in the absence of identifiable causes, ISS has long served as a diagnosis of exclusion. However, with the advent of next-generation sequencing, our understanding of the etiological landscape has significantly evolved. Recent studies have revealed that many children previously labeled as idiopathic actually harbor monogenic variants in genes related to the growth hormone-insulin-like growth factor axis, extracellular matrix components, or growth plate signaling pathways. This review integrates auxological assessment with current knowledge on molecular diagnostics to propose a more accurate and individualized approach to short stature. We examine emerging genotype-phenotype correlations, criteria for selecting candidates for genetic testing, and implications for recombinant human growth hormone therapy. Additionally, we advocate for a shift in clinical mindset: from a descriptive to a biologically grounded framework. ISS should be regarded as a transitional label pending further endocrine and genetic clarification. Recognizing this paradigm shift will improve diagnostic accuracy, personalize treatment strategies, and ultimately enhance care for children with growth failure in the genomic era.
特发性身材矮小（ISS）是儿科内分泌学中最常见但又最神秘的病症之一。传统上，ISS是在没有可识别病因的情况下根据体格测量参数定义的，长期以来一直作为排除性诊断。然而，随着下一代测序技术的出现，我们对病因格局的理解有了显著进展。最近的研究表明，许多以前被标记为特发性的儿童实际上在与生长激素 - 胰岛素样生长因子轴、细胞外基质成分或生长板信号通路相关的基因中存在单基因变异。本综述将体格评估与分子诊断的现有知识相结合，提出一种更准确、个性化的身材矮小处理方法。我们研究了新出现的基因型 - 表型相关性、选择基因检测候选者的标准以及对重组人生长激素治疗的影响。此外，我们主张临床思维的转变：从描述性框架转向基于生物学的框架。在进一步进行内分泌和遗传学明确之前，ISS应被视为一个过渡性标签。认识到这一范式转变将提高诊断准确性，使治疗策略个性化，并最终在基因组时代加强对生长发育迟缓儿童的护理。
