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

Abstract

Background and objectivesOsteogenesis 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.MethodsA 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.ResultsA 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).ConclusionsCardiovascular 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.

Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches

“…Rare instances of abrupt mortality from left ventricular rupture in asymptomatic OI patients highlight the possibility that reduced collagen type 1 in OI may lead to decreased tensile strength in the heart muscle and potential cardiac problems. 138 Alternatively, decreased levels of collagen type 1 in OI may be involved in the expansion of atria and ventricles, potentially leading to atrial arrhythmias and heart failure. 139 The likelihood of experiencing these arrhythmias has not been fully assessed.…”

“…Understanding how genotype and cardiovascular phenotype are related may aid in managing and advancing the understanding of the illness. 138 However, the observation that valve anomalies are less frequently seen in adults with OI than in children raises the possibility that patients with OI may develop cardiovascular illness as they age, necessitating evaluation of cardiovascular structure and function during long-term follow-up. Further evidence is required to establish the connection between the severity of OI and cardiac anomalies.…”

“…These findings suggest a potential association between OI and anatomical and functional alterations in the cardiovascular system. Rare instances of abrupt mortality from left ventricular rupture in asymptomatic OI patients highlight the possibility that reduced collagen type 1 in OI may lead to decreased tensile strength in the heart muscle and potential cardiac problems . Alternatively, decreased levels of collagen type 1 in OI may be involved in the expansion of atria and ventricles, potentially leading to atrial arrhythmias and heart failure .…”

“…Valvular disease and enlarged aortic diameter were the most diagnosed cardiovascular issues in patients with OI. Emerging evidence, especially in children with OI, , suggests a possible link between OI and cardiovascular problems.…”

“…Research has indicated that children with OI have a greater frequency of cardiovascular problems than children in the general population. , These anomalies may consist of functional deficits, structural flaws, and aberrant valve behavior . Studies have also explored the relationship between OI genotypes and cardiovascular problems in children, considering that different gene mutations can cause different types of OI.…”