An insulin-like growth factor-I receptor defect associated with short stature and impaired carbohydrate homeostasis in an Italian pedigree.

BACKGROUND: Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis.

METHODS: We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R mutation (p.Tyr387X): an 18-year-old male (index case), his sister and two paternal aunts.

RESULTS: All family members showed a variable degree of impairment in prenatal growth, with birth weight standard deviation scores (SDS) between -1.65 and -2.37 and birth length SDS between -1.78 and -3.08. Their postnatal growth was also impaired, with height SDS between -1.75 and -4.86. The index case presented high IGF-I levels during childhood and adolescence and delayed bone age. The index case and his two paternal aunts had impaired glucose tolerance (IGT) associated with a variable degree of alterations in insulin sensitivity and secretion. In contrast, the index case's sister, who had had IGT during pregnancy, showed normal glucose metabolism but reduced insulin sensitivity.

CONCLUSION: This is the first study showing an association between a novel IGF1R mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism.