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Observational Study
. 2025 Jan-Feb;28(1):24-30.
doi: 10.1177/10935266241272511. Epub 2024 Aug 27.

Case Series of 6 Fetuses With Osteogenesis Imperfecta Type II: A Retrospective Study of Heart Pathology

Sara J E Verdonk  1   2   3 , Silvia Storoni  1   2   3 , Lidiia Zhytnik  2   3   4   5   6 , Dimitra Micha  2   3   4   6 , Joost G van den Aardweg  7 , Otto Kamp  8 , Elisabeth M W Eekhoff  1   2   3   6 , Marianna Bugiani  9
Affiliations
Observational Study

Case Series of 6 Fetuses With Osteogenesis Imperfecta Type II: A Retrospective Study of Heart Pathology

Sara J E Verdonk et al. Pediatr Dev Pathol. 2025 Jan-Feb.

Abstract

Introduction: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility. While skeletal manifestations are well documented, few studies have explored the effect of OI on the fetal heart. This retrospective case series investigates cardiac pathology in OI type II fetuses, aiming to address this gap.

Methods: Medical records and autopsy reports of 6 genetically confirmed OI type II cases were examined. Fetuses had pathogenic variants in COL1A1 or PPIB, inducing structural defects in collagen type I. In addition to hematoxylin and eosin and Elastic van Gieson staining, the expression of collagen type I, COL1A1 and COL1A2 chains was examined by immunohistochemistry.

Results: Immunohistochemistry confirmed robust expression of collagen type I throughout the heart. Five fetuses had normal heart weight, while 1 had a low heart weight in the context of generalized growth retardation. None displayed structural heart anomalies.

Conclusion: This study reveals robust collagen type I expression in the hearts of OI type II fetuses without structural anomalies. We hypothesize that collagen type I abnormalities may not be causative factors for heart anomalies during early embryonic development. Instead, their impact may be conceivably related to an increased susceptibility to degenerative changes later in life.

Keywords: COL1A1; COL1A2; OI type II; collagen type I; heart pathology; osteogenesis imperfecta.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Collagen type I, COL1A1 and COL1A2 expression in the myocardial tissue of 6 OI type II fetuses investigated by immunohistochemistry. Collagen staining is shown in brown. Scale bar indicates 250 μm, and applies to all images. Gestational age is represented as weeks (w) + days.
Figure 2.
Figure 2.
Immunohistochemical staining of collagen type I, COL1A1, and COL1A2 in the heart of OI fetus 1 (14 weeks + 5 days). Collagen staining is depicted in brown, indicating the presence of collagen type I (and its chains) in the following areas: (A) atrioventricular valve, (C) aorta, (D) myocardium, (E) epicardium, (F) atrium, and (G) endocardium. Scale bars for each anatomical location are provided. Collagen type I was found throughout the heart (B), with enrichment observed at the epicardial and endocardial surfaces, as well as in the atrioventricular valve and aortic root.
See this image and copyright information in PMC

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