title: Diagnosis and management of disorders of IGF-I synthesis and action.
abstract: After a proper medical history, growth analysis and physical examination of a short child, followed by radiological and laboratory screening, the clinician may decide to perform genetic testing. We recently proposed several clinical algorithms that can be used to establish the diagnosis. GH insensitivity (primary IGF-I deficiency) can be caused by genetic defects in GHR, STAT5B, IGF1, IGFALS, which all have their specific clinical and biochemical characteristics. IGF-I resistance is seen in heterozygous defects of IGF1R. If besides short stature additional abnormalities are present, these should be matched with known dysmorphic syndromes. If no obvious candidate gene can be determined, a whole genome approach can be taken to check for deletions, duplications and/or uniparental disomies (SNP-array) or whole exome sequencing. Children with GHR defects, and presumably STAT5B and homozygous IGF1 defects, can be treated with rhlGF-I. Children with IGF1R defects and mild or heterozygous IGF1 defects respond to GH treatment.
authors.affiliation: Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands. j.m.wit@lumc.nl
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
mesh_terms: D002648:Child; D003940:Diagnostic Techniques, Endocrine; D004351:Drug Resistance / Q000235:genetics; D006130:Growth Disorders / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D046150:Laron Syndrome / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1