Effect of recombinant human insulin-like growth factor 1 therapy in a child with 3-M syndrome-1 with CUL 7 gene mutation

J Pediatr Endocrinol Metab. 2020 Aug 17;33(12):1609-1612. doi: 10.1515/jpem-2020-0278. Print 2020 Dec 16.


Objective: 3-M syndrome is characterized by severe short stature, syndromic features, and characteristic radiographic findings. Growth hormone (GH) has been used with variable success. Recombinant human insulin like growth factor-1 (rhIGF-1) has never been utilized.

Case presentation: We describe a child with severe growth retardation, macrocephaly, and skeletal abnormalities with evidence of GH insensitivity subsequently treated with rhIGF-1. He developed morbid obesity and comorbidities including voracious appetite, acanthosis nigricans, tonsillar hypertrophy, and severe obstructive sleep apnea with minimal height improvement. Genetic testing done at 11.5 years revealed a compound heterozygous mutation (c.2112G>A(p.W704X) and c.2559delC) in the CUL7 gene consistent with 3-M syndrome-1. rhIGF-1 therapy was discontinued.

Conclusions: This case highlights the novel use of rhIGF-1 therapy on a child with 3-M syndrome-1 with minimal height benefit but accelerated weight gain and serves as a reminder of the importance of re-evaluating therapy efficacy and side effect profile.

Keywords: 3-M syndrome; CUL-7 gene mutation; growth hormone; recombinant human insulin-like growth factor-1.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Cullin Proteins / genetics*
  • Dwarfism / drug therapy*
  • Dwarfism / etiology
  • Dwarfism / pathology
  • Growth Substances / therapeutic use*
  • Humans
  • Insulin-Like Growth Factor I / therapeutic use*
  • Male
  • Muscle Hypotonia / drug therapy*
  • Muscle Hypotonia / etiology
  • Muscle Hypotonia / pathology
  • Mutation*
  • Prognosis
  • Recombinant Proteins / therapeutic use*
  • Spine / abnormalities*
  • Spine / pathology


  • CUL7 protein, human
  • Cullin Proteins
  • Growth Substances
  • Recombinant Proteins
  • Insulin-Like Growth Factor I
  • mecasermin

Supplementary concepts

  • Miller-McKusick-Malvaux-Syndrome (3M Syndrome)