Department of Developmental Biology and Medicine, University of Manchester, Manchester M13 9PL, UK.
Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
J Clin Endocrinol Metab. 2023 Mar 10;108(4):1007-1017. doi: 10.1210/clinem/dgac637.
The first step in the evaluation of the short child is to decide whether growth parameters in the context of the history are abnormal or a variant of normal. If growth is considered abnormal, system and hormonal tests are likely to be required, followed by more directed testing, such as skeletal survey and/or genetic screening with karyotype or microarray. In a small percentage of short children in whom a diagnosis has not been reached, this will need to be followed by detailed genetic analysis; currently, exome sequencing using targeted panels relevant to the phenotype is the commonly used test. Clinical scenarios are presented that illustrate how such genetic testing can be used to establish a molecular diagnosis, and how that diagnosis contributes to the management of the short child. New genetic causes for short stature are being recognized on a frequent basis, while the clinical spectrum for known genes is being extended. We recommend that an international repository for short stature conditions is established for new findings to aid dissemination of knowledge, but also to help in the definition of the clinical spectrum both for new and established conditions.
评估身材矮小儿童的第一步是判断其生长参数在该病史背景下是异常的，还是正常变异。如果认为生长异常，可能需要进行系统和激素检测，然后进行更有针对性的检测，如骨骼检查和/或核型或微阵列遗传筛查。在一小部分未确诊的身材矮小儿童中，这将需要进行详细的基因分析；目前，使用与表型相关的靶向面板进行外显子组测序是常用的检测方法。本文提供了一些临床情况示例，说明了如何使用此类基因检测来确定分子诊断，以及该诊断如何有助于矮小儿童的管理。经常会发现新的导致身材矮小的遗传原因，而已知基因的临床谱也在不断扩展。我们建议为身材矮小症建立一个国际知识库，以帮助传播知识，同时也有助于为新的和已建立的病症定义临床谱。
