Growth failure: 'idiopathic' only after a detailed diagnostic evaluation

Abstract

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.

Keywords: genotyping; growth hormone therapy; idiopathic short stature; linear growth; short stature; small for gestational age.

Figure 1

Scheme for investigation of ISS and ‘idiopathic’ SGA giving equal status to clinical assessment, endocrine evaluation and genetic investigations (12, 91). CVS, cardiovascular system; Anti-TTG, anti-tissue transglutaminase; IGF-I-GT, IGF-I generation test; CGH-array, comparative genomic hybridisation; CNV, copy number variation.