Deciphering short stature in children

Abstract

Short stature is a common reason for referral to pediatric endocrinologists. Multiple factors, including genetic, prenatal, postnatal, and local environmental factors, can impair growth. The majority of children with short stature, which can be defined as a height less than 2 standard deviation score below the mean, are healthy. However, in some cases, they may have an underlying relevant disease; thus, the aim of clinical evaluation is to identify the subset of children with pathologic conditions, for example growth hormone deficiency or other hormonal abnormalities, Turner syndrome, inflammatory bowel disease, or celiac disease. Prompt identification and management of these children can prevent excessive short stature in adulthood. In addition, a thorough clinical assessment may allow evaluation of the severity of short stature and likely growth trajectory to identify the most effective interventions. Consequently, appropriate diagnosis of short stature should be performed as early as possible and personalized treatment should be started in a timely manner. An increase in knowledge and widespread availability of genetic and epigenetic testing in clinical practice in recent years has empowered the diagnostic process and appropriate treatment for short stature. Furthermore, novel treatment approaches that can be used both as diagnostic tools and as therapeutic agents have been developed. This article reviews the diagnostic approach to children with short stature, discusses the main causes of short stature in children, and reports current therapeutic approaches and possible future treatments.

Keywords: Anthropometric measurements; Auxology; Child; Growth hormone therapy; Height; Short stature; Growth.

Fig. 1.

GH-IGF-1 axis. GH, growth hormone; GHRH, GH releasing hormone; IGF-1, insulin-like growth factor-1; IGFBP, IGF-binding protein; ALS, acid-labile subunit. , stimulatory; , inhibitory.

Fig. 2.

Flow-chart for investigation of children with short stature. TSH, tyroid-stimulating hormone; IGF-1, insulinlike growth factor-1; GH, growth hormone; GHD, growth hormone deficiency; CDGP, constitutional delay of growth and puberty; ISS, idiopathic short stature. ^*Family and past medical history as: consanguinity, timing of puberty in the parents, birth history, abnormalities of fetal growth, perinatal complications, chronic disease, medication use, nutritional status, and psycho- social and cognitive development. ^**Using arm span, sitting height or upper-tolower segment ratios, body mass index, and measurement of head circumference (<4 years of age). ^***Blood count, erythrocyte sedimentation rate, creatinine, electrolytes, bicarbonate, calcium, phosphate, alkaline phosphatase, albumin, TSH, and free T4, screening for coeliac disease; karyotype in girls.