Mechanisms of in utero overgrowth

D'Ercole AJ. Mechanisms of in utero overgrowth. Acta Pædiatr 1999; Suppl 428: 31–6. Stockholm. ISSN 0803–5326
Determination of the mechanisms that lead to in utero overgrowth has proved elusive. Recently, however, our knowledge has significantly expanded as a result of the generation of experimental mouse models, engineered to disrupt the expression of one or more genes (knockout mice), and by detailed molecular and genetic analyses of infants and children with overgrowth syndromes. Studies of knockout mice have largely defined the essential roles of the insulin-like growth factors (IGF-I and IGF-II), insulin and their receptors in embryonic and fetal growth, and have provided compelling evidence that increased IGF-II gene expression and/or abundance can stimulate excessive fetal somatic growth. The IGF-II gene is usually expressed only by the paternally derived allele; however, when this imprinting is erased and IGF-II expression is biallelic, fetal overgrowth ensues. Such increased IGF-II expression would appear to explain the overgrowth in Beckwith-Wiedemann syndrome. Using the information gathered from knockout mice as a guide to human studies, detailed genetic investigations are likely to unravel the mechanisms behind other human overgrowth syndromes. □ Beckwith-Wiedemann syndrome, gene expression, imprinting, insulin, insulin-like growth factors, insulin-like growth factor receptors, insulin receptor, overgrowth syndromes