Cardiovascular abnormalities and its correlation with genotypes of children with osteogenesis imperfecta

Background and objectives: Osteogenesis imperfecta (OI) is a rare disorder of abnormal production or modification of type I collagen, which is caused by mutations in COL1A1, COL1A2 or other genes. We investigate the cardiac abnormalities and its correlation with pathogenic mutations in OI children.

Methods: A cross-sectional comparative study was completed in a relatively large sample of OI children, who were matched in body surface area (BSA) with healthy controls. All echocardiography was performed by experienced cardiologists using Vivid 7 equipment (GE Medical Systems, Horton, Norway). The resting standard 12-lead electrocardiogram (ECG) were obtained in OI patients by FX-8600 machine. Skeletal phenotypes of OI patients were evaluated, including information of bone fractures, deformities, motility, and bone mineral density (BMD). Pathogenic mutations of OI were detected by a next-generation sequencing panel and confirmed by Sanger sequencing.

Results: A total of 69 OI children and 42 healthy children matched in BSA were enrolled. Abnormalities of echocardiography were found in 6 OI children, including enlarged left atrium (n=5), increased internal diameter of the left ventricle (n=1), who all carried the COL1A1 mutation. Mild regurgitation of mitral or tricuspid valves was observed in 26 OI patients. Abnormal ECG manifestations were found in 8 OI children, including deep Q wave, T wave change, premature ventricular complexes, short P-R interval, incomplete bundle branch block and high voltage of left ventricular. Compared with healthy controls, OI children had significant larger values in the main pulmonary artery (1.84 vs 1.60 cm, P < 0.01), left atrial diameter (2.58 vs 2.11 cm, P < 0.001), left ventricular internal dimension at end-diastolic (LVEDd) (3.85 vs 3.50 cm, P < 0.05) and lower left ventricular ejection fraction (LVEF) (68.40% vs 71.74%, P < 0.01). Moreover, OI patients with COL1A1 mutation tended to have greater main pulmonary artery, larger diameters of left atrial and LVEDd, and lower LVEF than healthy controls. COL1A1 mutation was correlated to dilated MPA (β = 1.557, P < 0.01), LAD (β = 3.915, P < 0.001), and LVEDd (β = 2.714, P < 0.01), and decreased LVEF (β = -3.249, P < 0.01).

Conclusions: Cardiovascular alterations were identified in OI children, including increased dimensions of the main pulmonary artery and left chamber, and low LVEF. The cardiovascular abnormalities seemed to be correlated to COL1A1 mutation and defects of type I collagen, which expanded our understandings of the cardiac phenotypes of OI children.