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.

Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database

“…The GH-IGF-1 axis is the primary key to the endocrine system that controls linear growth during childhood [ 30 ]. GH regulates IGF-I release by acting on the liver, which modulates bone length during childhood [ 7 , 31 ]. IGF-I secretion does not depend on diurnal variation or pulsatility [ 6 ].…”

“…GH binds to the GH receptor and stimulates STAT5b activation in the hepatocytes [ 27 ]. Subsequently, it stimulates the production and secretion of not only IGF-I but also IGFBP-3 from the liver [ 7 ]. Serum levels of IGF-I and IGFBP-3 are even more important in GH/IGF-I assessments for older children and children younger than 3 years of age [ 7 ].…”

“…Subsequently, it stimulates the production and secretion of not only IGF-I but also IGFBP-3 from the liver [ 7 ]. Serum levels of IGF-I and IGFBP-3 are even more important in GH/IGF-I assessments for older children and children younger than 3 years of age [ 7 ]. However, many hormones control circulating IGF-1 levels, such as insulin [ 41 ], thyroid hormone [ 42 ], and sex hormones [ 43 ].…”

“…Serum IGF-I and IGF binding protein (IGFBP)-3 levels depend on GH levels under normal physiological conditions [ 7 ]. IGF-I concentration is the most widely used parameter for monitoring and adjusting rhGH therapy [ 8 ].…”

Clinical relevance of targeted exome sequencing in patients with rare syndromic short stature

“…The identification of pathogenic mutations has important implications; for example, a genetic diagnosis avoids unnecessary investigations and treatment, allows appropriate genetic counseling and the identification of comorbidities in syndromic SS, and may also lead to the earlier initiation of therapy [ 7 ]. In particular, if SS is related to dysmorphic features, a syndromic condition should be suspected and a genetic test should be conducted [ 8 ]. Exome sequencing methods, such as targeted exome sequencing (TES) and whole exome sequencing (WES), can be useful in clinical practice for the genetic diagnosis of diseases associated with SS [ 9 , 10 ].…”