Rapaport Robert, Wit Jan M, Savage Martin O
Division of Pediatric Endocrinology & Diabetes, Mount Sinai Kravis Children's Hospital and Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Endocr Connect. 2021 Mar;10(3):R125-R138. doi: 10.1530/EC-20-0585.
The terms 'idiopathic short stature' (ISS) and 'small for gestational age' (SGA) were first used in the 1970s and 1980s. ISS described non-syndromic short children with undefined aetiology who did not have growth hormone (GH) deficiency, chromosomal defects, chronic illness, dysmorphic features or low birth weight. Despite originating in the pre-molecular era, ISS is still used as a diagnostic label today. The term 'SGA' was adopted by paediatric endocrinologists to describe children born with low birth weight and/or length, some of whom may experience lack of catch-up growth and present with short stature. GH treatment was approved by the FDA for short children born SGA in 2001, and by the EMA in 2003, and for the treatment of ISS in the US, but not Europe, in 2003. These approvals strengthened the terms 'SGA' and 'ISS' as clinical entities. While clinical and hormonal diagnostic techniques remain important, it is the emergence of genetic investigations that have led to numerous molecular discoveries in both ISS and SGA subjects. The primary message of this article is that the labels ISS and SGA are not definitive diagnoses. We propose that the three disciplines of clinical evaluation, hormonal investigation and genetic sequencing should have equal status in the hierarchy of short stature assessments and should complement each other to identify the true pathogenesis in poorly growing patients.
“特发性身材矮小”（ISS）和“小于胎龄儿”（SGA）这两个术语最早在20世纪70年代和80年代被使用。ISS描述的是病因不明的非综合征性身材矮小儿童，他们没有生长激素（GH）缺乏、染色体缺陷、慢性病、畸形特征或低出生体重。尽管起源于分子时代之前，但ISS如今仍被用作诊断标签。“小于胎龄儿”这一术语被儿科内分泌学家采用，用于描述出生时体重和/或身长较低的儿童，其中一些儿童可能会出现追赶生长不足并表现为身材矮小。2001年，美国食品药品监督管理局（FDA）批准生长激素用于治疗小于胎龄儿出生的矮小儿童，2003年欧洲药品管理局（EMA）批准，2003年美国批准生长激素用于治疗ISS，但欧洲未批准。这些批准强化了“小于胎龄儿”和“特发性身材矮小”作为临床实体的概念。虽然临床和激素诊断技术仍然很重要，但正是基因研究的出现，才在特发性身材矮小和小于胎龄儿个体中带来了众多分子发现。本文的主要观点是，“特发性身材矮小”和“小于胎龄儿”这两个标签并非确定性诊断。我们建议，临床评估、激素检查和基因测序这三个学科在身材矮小评估体系中应具有同等地位，并且应相互补充，以确定生长发育不良患者的真正发病机制。
