Abstract
Osteogenesis Imperfecta (OI) is a rare congenital disorder of bone fragility. Majority of OI cases are caused by loss of function or missense pathogenic variants in the COL1A1/2 genes. In addition to fractures, patients suffer from different, mainly long bone, skeletal deformities. OI patients might develop chest deformities (pectus carinatum (PC) or excavatum (PE)) of different severity, which can tend to formation of cardiopulmonary complications. The main aim of current study was to investigate chest deformities in 165 patients from the OI database of Tartu University Department of Traumatology and Orthopedics. We have compared severity of the chest deformity with OI type, genotype and sex of the patient. Data of OI genotypes was recruited from previous Sanger sequencing mutational analysis of the COL1A1/2 genes. Chest deformity was examined with observation. Significance of correlations was confirmed with Fisher’s test. 55.65% (92/165) of patients suffered from moderate to severe chest deformities. Severity of deformation correlated with OI type (P-value=0.0002e-12). Chest deformities did not reveal correlation with affected gene (P-value=0.7205) or sex (P-value=0.183). However, among COL1A1/2 cases, severity of the chest deformity depended on the collagen defect type (P-value=0.0006). Extreme chest deformities were present in 22.82% (21/92) cases. Four (19.05%) of them were PE (all present in male patients) and 17 (80.95%) PC (9 males and 8 females). Out of non-COL1A1/2 OI cases, all patients with extreme chest deformities were OI type 3. Among collagen OI cases were types 1 (PE), 3 (PE, PC) and 4 (PC). Especially severe PC cases were caused by following mutations: COL1A1 c.1981G>C p.(Gly661Ser), COL1A2 c.792+1G (haploinsufficiency), COL1A1 c.1350G>C p.(Glu450Asp). In contrast to cases of PE and PC of unknown etiology, OI-related PE and PC do not correlate with sex. Chest deformities arise with similar frequency among collagen-related and non-COL1A1/2 OI patients. More severe chest deformities were common among OI type 3 patients, and patients with missense, compared to loss of function COL1A1/2 pathogenic variants. Despite carrying of the same OI pathogenic variant, development of the PE and PC differs among patients, what underlines presence of additional factors affecting rib cage deformity development in OI patients.