Etiology and diagnostic approach of growth failure in children born small for gestational age (SGA) with persistent short stature in childhood (SGA-SS)
Abstract
Approximately 3-5% of all neonates are born with a birth weight and/or birth length of below-2 SD of the gestational age-specific normative values. They are assigned as being small for gestational age (SGA).
About 90% of them will experience catch-up growth within the first two years of life. The additional 10%, who fail to catch-up and remain short during childhood, are referred as "small for gestational age-short stature" (SGA-SS) and fulfil arbitrary criteria for growth hormone (GH) administration.
The etiology of SGA-SS is heterogeneous. Some children have specific facial and other phenotypic features that allow targeted genetic testing; in others, the genetic testing might be more challenging.
Significant genetic causes of SGA-SS include abnormal methylation patterns leading to Silver-Russell syndrome, de-fects of the GH - IGF-1 - growth plate axis, defective paracrine regulation of the chondrocyte, and abnormal formation of growth plate extracellular matrix. Identification of the genetic defect allows understanding the underlying pathophysiological mechanism of short stature and its inheritance pattern, facilitates a targeted search for comorbidities, and partly predicts the effect of treatment with growth hormone.