Cross-sectional and longitudinal growth patterns in osteogenesis imperfecta: implications for clinical care.

BACKGROUND: There is strikingly limited information on linear growth and weight in the different types of osteogenesis imperfecta (OI). Here, we define growth patterns further with the intent of implementing appropriate adaptations proactively. METHODS: We report cross-sectional anthropometric data for 343 subjects with different OI types (144 children, 199 adults). Longitudinal height data for 36 children (18 girls, 18 boys) with OI type I and 10 children (8 girls, 2 boys) with OI type III were obtained. RESULTS: In all cases, the height Z-scores were negatively impacted, and final height Z-scores were impacted the most. In type I, the growth velocities taper near puberty, and there is a blunted pubertal growth spurt. The growth velocities of children with type III decelerate before age 5 y; poor growth continues without an obvious pubertal growth spurt. Obesity is a concern for all patients with OI, with type III patients being the most affected. CONCLUSION: The linear growth patterns, in addition to the marked increase in weight over time, indicate a need for lifestyle modifications early in childhood, especially a need for weight control. Further definition of the anthropometric measures in OI enables patients to begin modifications as early as possible.

Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation.

In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5' untranslated region (5'UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.-14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation.