Single gene mutations causing SGA.
The growth hormone-insulin-like growth factor-I (GH-IGF-I) axis plays a key role in intra-uterine growth and development. This review will describe the consequences of genetic defects in various components of the GH-IGF-I axis on intra-uterine growth and development. Animal knockout experiments have provided evidence for the GH-independent secretion of IGF-I and its effect in utero. Reports of patients with a deletion or mutation of the IGF-I and IGF1R genes have provided insight into the role of intra-uterine IGF-I in the human. Homozygous defects of the IGF-I gene have dramatic effects on intra-uterine growth and development, whereas heterozygous defects of the IGF1R gene have a more variable clinical presentation. The phenotype in relation to the genotype of the different disorders will be reviewed in this chapter.
Department of Paediatrics, J6-S, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands. m.walenkamp@lumc.nl
Marie J E
MJ
Walenkamp
Jan M
JM
Wit
D000818:Animals; D001921:Brain / Q000254:growth & development; D001933:Brain Stem / Q000254:growth & development; D003241:Consanguinity; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000235:genetics; D006130:Growth Disorders / Q000175:diagnosis / Q000235:genetics; D013006:Growth Hormone / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D018969:Insulin-Like Growth Factor Binding Proteins / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011247:Pregnancy; D011986:Receptors, Somatotropin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone