IGF2, a major actor which stimulates feta growth, is located within the imprinted 11p15 region, and 11p paternal duplications are usually associated with Beckwith Wiedemann syndrome, a rare condition usually associated with overgrowth. The IGF type 1 receptor binds both IGF-I and IGF-II to promotes cell proliferation and growth, and the IGF1R gene is located at chromosome 15q. Patients with deletions or mutations of IGF1R usually present with intrauterine and postnatal growth retardation.
We report an original association of complex genetic defects in a patient carrying both an 11p paternal duplication, and a 15q terminal deletion, including the IGF1R. Conversely to patients with IGF1R defects, the patient presented with normal birth parameters. However she presented with short stature after birth, microcephaly, intellectual disability and elevated IGF1 serum concentrations as usually described in patients with IGF1R anomalies.
This rare case allows a better comprehension of the IGF system in the pathophysiology of growth. We hypothesize that overexpression of IGF-II due to the 11p15 duplication, and the IGF1R defect may have compensated each other during fetal life. As postnatal growth was altered, this supports the hypothesis that the role of IGF-II is less important in post-natal growth, leaving IGF-I and growth hormone as the main actors after birth.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology