Insulin-like Growth Factor I, Resistance to

Alternative Names

  • IGF-I Resistance
  • Somatomedin, End-Organ Insensitivity to
  • Somatomedin-C, Resistance to
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Disorders of other endocrine glands

OMIM Number

270450

Mode of Inheritance

Autosomal dominant or autosomal recessive

Gene Map Locus

15q26.3

Description

Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced in response to growth hormone (GH). Although it is primarily a mediator of GH stimulated somatic growth, IGF-I has its own anabolic responses in many cells and tissues. IGF-I resistance can lead to both intrauterine and postnatal growth retardation. Affected individuals are characterised by short stature, intellectual deficit, microcephaly, delayed bone age and dysmorphism.

Studies have shown IGF-I resistance to follow both autosomal dominant and autosomal recessive inheritance pattern. Several genetic defects could cause IGF-I resistance. These include: ring chromosome 15; deletions in the 15q region comprising the IGF1R gene (15q26.3); or IGF1R gene mutations. Diagnosis of IGF-I resistance is also based on detection of these defects through karyotyping or direct sequencing.

IGF1R gene encodes insulin-like growth factor 1 receptor, which is a transmembrane protein involved in signaling pathways that regulate cell growth and cell survival. The exact role of IGF1R in conferring IGF-I resistance and subsequent effect on growth delay is not clearly understood. However, mutations in the IGF1R gene are known to reduce the number of IGF1 receptors in affected individuals. This can interfere with the normal cellular response pattern of IGF1 resulting in growth delay.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
270450.1.1LebanonFemaleYesYes Perimembranous ventricular septal defect...NM_000875.5:c.119G>THomozygousAutosomal, RecessiveGannagé-Yared MH et al. 2012 Proband
270450.2.1LebanonMaleYesYes Intrauterine growth retardation; Postna...NM_000875.4:c.361G>A, NM_000875.4:c.700G>AHeterozygousAutosomal, RecessiveFang et al. 2012 Proband. Onset of di...
270450.2.2LebanonFemaleYesYes Intrauterine growth retardation; Postna...NM_000875.4:c.361G>A, NM_000875.4:c.700G>AHeterozygousAutosomal, RecessiveFang et al. 2012 Sister of patient 27...
270450.3.1Saudi ArabiaFemaleYesYes Lissencephaly; Abnormality of neuronal m...NM_000618.5:c.292C>THomozygousAutosomal, RecessiveShaheen et al. 2019; Shaheen et al. 2014
270450.3.2Saudi ArabiaMaleYesYes Short statureNM_000618.5:c.292C>THomozygousAutosomal, RecessiveShaheen et al. 2019; Shaheen et al. 2014 Relative of 270450.3...

Other Reports

United Arab Emirates

Cottrell et al. (2020) described an Emirati male patient who was born small for getational age and continued to have a short stature. He was found to carry a maternally inherited 7q21 duplication and a paternally inherited Xp22 duplication. 

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