Normal intelligence with severe insulin-like growth factor I deficiency due to growth hormone receptor deficiency: a controlled study in a genetically homogeneous population

J Clin Endocrinol Metab. 1998 Jun;83(6):1953-8. doi: 10.1210/jcem.83.6.4863.


Superior school performance was reported for 52 Ecuadorian probands with severe deficiency of insulin-like growth factor I (IGF-I) due to GH receptor deficiency (GHRD) resulting from homozygosity for the E180 splice mutation of the GHR. In contrast, subnormal intelligence was reported in a study of 18 genetically heterogeneous Israeli patients, attributed to frequent hypoglycemia or IGF-I dependence of brain development. This study is the first controlled evaluation of the intellectual ability of patients with GHRD. We compared the intelligence of 18 patients of school age (mean +/- SD age, 11.5 +/- 2.8 yr), 42 of their relatives (11.5 +/- 2.8 yr), and 28 community controls (10.0 +/- 0.8 yr), using a battery of intelligence tests that have been validated in cross-cultural research, designed to minimize the effects of physical size, motor coordination, and cultural background. Because all patients had the same GHR mutation, for which the carrier state could be determined, this study also investigated whether heterozygosity for mutation of the GHR among unaffected relatives is associated with intelligence. The intellectual ability of the patients with GHRD was not significantly different from that of their relatives (P > 0.05) on the psychometric tests of intelligence and was comparable to that of the community controls on the chronometric tests. Homozygosity or heterozygosity for the mutation in the GHR gene common to Ecuadorian patients was unrelated to intelligence (P > 0.05). These results indicate that the gene defect causing GHRD is not related to intelligence in the Ecuadorian population. They also indicate that GH-induced IGF-I production is not required for normal brain growth in utero or for postnatal intellectual development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Cognition
  • Ecuador
  • Female
  • Homozygote
  • Humans
  • Insulin-Like Growth Factor I / deficiency*
  • Intelligence*
  • Male
  • Mutation*
  • RNA Splicing / genetics
  • Receptors, Somatotropin / deficiency*
  • Receptors, Somatotropin / genetics*


  • Receptors, Somatotropin
  • Insulin-Like Growth Factor I