Ann Pediatr Endocrinol Metab.  2021 Dec;26(4):218-226. 10.6065/apem.2142208.104.

Balanced assessment of growth disorders using clinical, endocrinological, and genetic approaches

• Savage MO
• Storr HL

• KMID: 2523827
• DOI: http://doi.org/10.6065/apem.2142208.104

Abstract

Determining the pathogenesis of pediatric growth disorders is often challenging. In many cases, no pathogenesis is identified, and a designation of idiopathic short stature is used. The investigation of short stature requires a combination of clinical, endocrinological, and genetic evaluation. The techniques used are described, with equal importance being given to each of the 3 approaches. Clinical skills are essential to elicit an accurate history, family pedigree, and symptoms of body system dysfunction. Endocrine assessment requires hormonal determination for the diagnosis of hormone deficiency and initiation of successful replacement therapy. Genetic analysis has added a new dimension to the investigation of short stature and now uses next-generation sequencing with a candidate gene approach to confirm probable recognizable monogenic disorders and exome sequencing for complex phenotypes of unknown origin. Using the 3 approaches of clinical, endocrine, and genetic probes with equal status in the hierarchy of investigational variables provides the clinician with the highest chance of identifying the correct causative pathogenetic mechanism in a child presenting with short stature of unknown origin.

Keyword

Growth; Genetics; Evaluation; Growth hormone; Short stature

Figure

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  Fig. 1. Scheme for clinical assessment of short stature.

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  Fig. 2. Biochemical, endocrinological, and radiological assessment of the child with short stature. ESR, erythrocyte sedimentation rate; Alk Phos, alkaline phosphatase; FT4, Free thyroxine; TSH, thyroid-stimulating hormone; IGF-1, insulin-like growth factor-I; TTG, tissue transglutaminase; IGFBP-3, insulin-like growth factor binding protein-3; GHBP, growth hormone binding protein; ALS, acid labile subunit; MRI, magnetic resonance imaging; GH, growth hormone.

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  Fig. 3. Proposed scheme for genetic investigations of the child with short stature. SNP, single nucleotide polymorphism; CGH, comparative genomic hybridization; CNV, copy number variation; UPD, uniparental disomy.

Reference

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