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Longitudinal growth curves for children with classical osteogenesis imperfecta (types III and IV) caused by
Lauren A Barber1,2, Craig Abbott3, Vihang Nakhate1,4
1Section on Heritable Disorders of Bone and Extracellular Matrix, NICHD, NIH, Bethesda, MD, USA.
Insights
Growth charts for Osteogenesis Imperfecta (OI) types III and IV are now available. OI type significantly impacts growth, more than gender, with distinct BMI shifts compared to the general population.
Area of Science:
- Pediatrics
- Genetics
- Endocrinology
Background:
- Osteogenesis Imperfecta (OI) types III and IV are characterized by significant growth deficiency.
- Pathogenic variants in type I collagen are the underlying cause of these OI types.
- There is a clinical need for OI-specific longitudinal growth charts for accurate patient management.
Purpose of the Study:
- To develop and present OI-specific longitudinal growth charts for children with OI types III and IV.
- To analyze the influence of gender, OI type, and specific collagen gene variants on growth parameters.
Main Methods:
- Longitudinal data (length, weight, head circumference, BMI) were collected from 100 children with OI types III/IV.
- Multilevel modeling was used to assess the effects of gender, OI type, and pathogenic variants.
- Generalized additive models for location, scale, and shape (GAMLSS) were employed to construct OI-specific centile curves.
Main Results:
- OI type and gender significantly affect stature, with OI type also impacting weight.
- Head circumference showed no significant differences based on gender, OI type, or mutated gene.
- Length curves for OI types III and IV overlap; type IV curves approach general population curves at the 95th centile.
- A pubertal growth spurt is typically absent or blunted in OI types III/IV.
- Body mass index (BMI) centile curves for OI types III/IV are notably higher than US CDC curves.
Conclusions:
- OI type is a more significant factor in growth than gender for OI types III and IV.
- Growth curves do not differ between COL1A1 and COL1A2 pathogenic variants.
- The study provides essential OI-specific growth curves for types III and IV, aiding clinical care.
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.
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