AUTHOR=Zhao Dichen , Liu Yongtai , Liu Jidong , Hu Jing , Zhang Qian , Wang Ou , Jiang Yan , Xia Weibo , Xing Xiaoping , Li Mei 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1004946

DOI=10.3389/fendo.2022.1004946

ISSN=1664-2392

ABSTRACT=<sec><title>Background and objectives</title><p>Osteogenesis imperfecta (OI) is a rare disorder of abnormal production or modification of type I collagen, which is caused by mutations in <italic>COL1A1</italic>, <italic>COL1A2</italic> or other genes. We investigate the cardiac abnormalities and its correlation with pathogenic mutations in OI children.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 <italic>COL1A1</italic> 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, <italic>P</italic> &lt; 0.01), left atrial diameter (2.58 vs 2.11 cm, <italic>P</italic> &lt; 0.001), left ventricular internal dimension at end-diastolic (LVEDd) (3.85 vs 3.50 cm, <italic>P</italic> &lt; 0.05) and lower left ventricular ejection fraction (LVEF) (68.40% vs 71.74%, <italic>P</italic> &lt; 0.01). Moreover, OI patients with <italic>COL1A1</italic> mutation tended to have greater main pulmonary artery, larger diameters of left atrial and LVEDd, and lower LVEF than healthy controls. <italic>COL1A1</italic> mutation was correlated to dilated MPA (β = 1.557, <italic>P</italic> &lt; 0.01), LAD (β = 3.915, <italic>P</italic> &lt; 0.001), and LVEDd (β = 2.714, <italic>P</italic> &lt; 0.01), and decreased LVEF (β = -3.249, <italic>P</italic> &lt; 0.01).</p></sec><sec><title>Conclusions</title><p>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 <italic>COL1A1</italic> mutation and defects of type I collagen, which expanded our understandings of the cardiac phenotypes of OI children.</p></sec>