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.