Phenotypic Features and Response to GH Treatment of Patients With a Molecular Defect of the IGF-1 Receptor

J Clin Endocrinol Metab. 2019 Aug 1;104(8):3157-3171. doi: 10.1210/jc.2018-02065.

Abstract

Context: The phenotype and response to GH treatment of children with an IGF1R defect is insufficiently known.

Objective: To develop a clinical score for selecting children with short stature for genetic testing and evaluate the efficacy of treatment.

Design and setting: Case series with an IGF1R defect identified in a university genetic laboratory.

Patients and interventions: Of all patients with sufficient clinical data, 18 had (likely) pathogenic mutations (group 1) and 7 had 15q deletions including IGF1R (group 2); 19 patients were treated with GH.

Main outcome measures: Phenotype and response to GH treatment.

Results: In groups 1 and 2, mean (range) birth weight, length, and head circumference (HC) SD scores (SDSs) were -2.1 (-3.7 to -0.4), -2.7 (-5.0 to -1.0), and -1.6 (-3.0 to 0.0), respectively. At presentation, height, HC, and serum IGF-1 SDSs were -3.0 (-5.5 to -1.7), -2.5 (-4.2 to -0.5), and +1.2 (-1.3 to 3.2), respectively. Feeding problems were reported in 15 of 19 patients. A clinical score with 76% sensitivity is proposed. After 3 years of GH treatment [1.1 (0.2) mg/m2/d] height gain in groups 1 (n = 12) and 2 (n = 7) was 0.9 SDS and 1.3 SDS (at a mean IGF-1 of 3.5 SDS), less than reported for small for gestational age (1.8 SDS).

Conclusion: A clinical score encompassing birth weight and/or length, short stature, microcephaly, and IGF-1 is useful for selecting patients for IGF1R analysis. Feeding problems are common and the growth response to GH treatment is moderate.

MeSH terms

  • Adolescent
  • Adult
  • Body Height / drug effects
  • Child
  • Child, Preschool
  • Female
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Infant, Small for Gestational Age / growth & development
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Mutation*
  • Phenotype
  • Receptor, IGF Type 1 / genetics*
  • Retrospective Studies
  • Young Adult

Substances

  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1