Longitudinal growth curves for children with classical osteogenesis imperfecta (types III and IV) caused by structural pathogenic variants in type I collagen

Genet Med. 2019 May;21(5):1233-1239. doi: 10.1038/s41436-018-0307-y. Epub 2018 Oct 1.


Purpose: Growth deficiency is a cardinal feature of osteogenesis imperfecta (OI) types III and IV, caused by pathogenic variants in type I collagen. OI-specific longitudinal growth charts are needed for patient care.

Methods: We compiled longitudinal length, weight, head circumference, and body mass index (BMI) data from 100 children with types III and IV OI and known type I collagen pathogenic variants. Effects of gender, OI type, and pathogenic variant were examined using multilevel modeling. OI-specific centile curves were constructed using generalized additive model for location, scale, and shape (GAMLSS).

Results: OI type and gender, but not the specific mutated collagen gene, significantly affect stature, but only OI type affects weight. Head circumference was not significantly different by gender, type, or mutated gene. In both genders, length curves for types III and IV OI overlap and the type IV 95th centile curve overlaps the lower US Centers for Disease Control and Prevention (CDC) curves for the general population. A pubertal growth spurt is generally absent or blunted in types III/IV OI. The body mass index 50th and 95th centile curves are distinctly shifted above respective US CDC curves in both genders.

Conclusions: OI type is a stronger contributing factor than gender for OI growth, while curves do not differ for COL1A1 versus COL1A2 pathogenic variants. Types III and IV OI-specific growth curves are presented.

Keywords: growth curves; osteogenesis imperfecta; type III OI; type IV OI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Body Height
  • Body Mass Index
  • Body Size / genetics*
  • Body Weights and Measures
  • Child
  • Child Development / physiology
  • Child, Preschool
  • Collagen Type I / genetics*
  • Collagen Type I / metabolism
  • Female
  • Humans
  • Infant
  • Longitudinal Studies
  • Male
  • Osteogenesis Imperfecta / genetics*


  • Collagen Type I

Supplementary concepts

  • Osteogenesis imperfecta, type 3