Willems M, Amouroux C, Barat-Houari M, Salles J-P, Edouard T
Medical Genetic Department for Rare Diseases and Personalised Medicine, Reference Centre AD SOOR, AnDDI-RARE, Competence Centre for Rare Skeletal Disorders, OSCAR Network, Inserm U1298, INM, Arnaud de Villeneuve Hospital and University of Montpellier, Montpellier, France.
Paediatric Endocrine Unit, Competence Centre for Rare Diseases of Calcium and Phosphate Metabolism, OSCAR Network, Arnaud de Villeneuve Hospital and University of Montpellier, Montpellier, France.
Arch Pediatr. 2022 Feb;28(8S1):8S27-8S32. doi: 10.1016/S0929-693X(22)00040-9.
Statural growth is underpinned by development of the growth plate during the process of endochondral ossification, which is strongly regulated by numerous local factors (intracellular, paracrine and extracellular matrix factors) and systemic factors (nutrition, hormones, proinflammatory cytokines and extracellular fluids). This explains why growth retardation can be associated with numerous pathologies, particularly genetic syndromes, hormonal or inflammatory conditions, or gastrointestinal disorders having a nutritional impact. However, in most cases (80%), no specific aetiology is found after clinical investigation and conventional additional tests have been carried out. In such cases, "idiopathic" short stature is diagnosed, which includes patients presenting with constitutional delay of growth and development and familial short stature, but also patients with very subtle constitutional skeletal dysplasia which are not easily identifiable. In recent years, new methods of genetic investigation (e.g. gene panels, exome or genome sequencing) have made it possible to identify many genetic variants associated with apparently isolated short stature. Indeed, it is still difficult to estimate the proportion of patients presenting with idiopathic short stature for which a molecular diagnosis of monogenic conditions could be made. This estimate varies hugely depending on the thoroughness of the clinical, laboratory and radiological assessments performed prior to molecular analysis, since retrospective analysis of positive cases usually reveals subtle signs of underlying syndromes or rare skeletal disorders. Molecular diagnosis in children is important to be able to offer genetic counselling and to organise patient management. Moreover, improved understanding of the molecular basis of these cases of short stature opens up numerous possibilities for more specific treatments targeting the growth plate. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.
身高增长以内软骨成骨过程中生长板的发育为基础，这一过程受到多种局部因素（细胞内、旁分泌和细胞外基质因素）和全身因素（营养、激素、促炎细胞因子和细胞外液）的强烈调节。这就解释了为什么生长迟缓可能与多种疾病相关，特别是遗传综合征、激素或炎症性疾病，或具有营养影响的胃肠道疾病。然而，在大多数情况下（80%），临床调查和常规附加检查后未发现特定病因。在这种情况下，诊断为“特发性”身材矮小，其中包括生长发育体质性延迟和家族性身材矮小的患者，也包括具有非常细微的体质性骨骼发育异常且不易识别的患者。近年来，新的基因检测方法（如基因panel、外显子组或基因组测序）使得识别许多与明显孤立性身材矮小相关的基因变异成为可能。事实上，对于特发性身材矮小患者中能够做出单基因疾病分子诊断的比例仍难以估计。这一估计差异很大，取决于分子分析前进行的临床、实验室和放射学评估的彻底程度，因为对阳性病例的回顾性分析通常会揭示潜在综合征或罕见骨骼疾病的细微迹象。儿童的分子诊断对于能够提供遗传咨询和组织患者管理很重要。此外，对这些身材矮小病例分子基础的更好理解为针对生长板的更特异性治疗开辟了许多可能性。©️ 2022法国儿科学会。由爱思唯尔马松出版社出版。保留所有权利。
