THE LITTLE WOMEN OF LOJA - GROWTH-HORMONE RECEPTOR DEFICIENCY IN AN INBRED POPULATION OF SOUTHERN ECUADOR

Background and Methods. Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism. Result. Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients' heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 μg per liter) and normal to moderately elevated in the adults. The serum level of growth hormone—binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low — ≤7 μg per liter in the children and ≤66 μg per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone—dependent IGF-binding protein-3 were also low. Conclusion. We describe an inbred population with a high incidence of growth hormone—receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males. (N Engl J Med 1990; 323: 1367–74.). © 1990, Massachusetts Medical Society. All rights reserved.