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CHAPTER
34
Cardiovascular Disease in Osteogenesis
Imperfecta
Daniel P. Judge
Johns Hopkins University School of Medicine, Baltimore, MD, USA
INTRODUCTION
than right-sided (tricuspid and pulmonic) valve dis-
ease. Hortop and colleagues investigated a cohort of 109
people with OI from 66 separate families for cardiovas-
cular disease using M-mode echocardiography.
2
Despite
inherent technical limitations of this early form of cardiac
imaging, they were able to identify two people with aor-
tic regurgitation and one person with aortic stenosis. The
incidence of mitral valve prolapse was not discernibly
different from population-based studies among controls.
2
Migliaccio and colleagues reported their more extensive
echocardiographic analysis of 40 individuals with OI
(types I, III and IV), including 21 women and 19 men.
48
They found that although valve regurgitation was typi-
cally mild, it was widely prevalent among these patients;
only 5% were reported as having normal cardiac valves.
They found mitral and tricuspid regurgitation in 30%,
mitral regurgitation (MR) alone in 25%, MR and aor-
tic regurgitation (AR) in 10% and regurgitation of the
mitral, tricuspid and aortic valves in the remaining 30%
of this cohort.
48
A population-based study of adults with
OI in Norway involved 99 of the 154 individuals in that
country registered with the National Resource Centre
for Rare Disorders, 98 of whom met criteria for subtype
classification of OI.
3
There were 57 women and 41 men
aged 25-83 years, of whom 77 had type I, 10 had type III
and 11 had type IV OI. Echocardiography demonstrated
AR of mild severity in 10.1% and of moderate severity in
another 10.1% compared to none of the controls. A mild
degree of MR was common in both OI cases and con-
trols (57.5 vs. 61.5%, respectively), though moderate MR
was more common in OI than in controls (7.1% vs. 0%,
respectively).
Developmental studies in mice have shown
Col1a1
and
Col1a2
are highly expressed in the endocardial
In contrast with the skeletal manifestations of osteo-
genesis imperfecta (OI), the cardiovascular features
are typically more subtle and less frequently recog-
nized. However, this aspect of OI is among the most
life-threatening. The exact incidence and risk of cardio-
vascular disease for individuals with OI is currently
unknown. Type I collagens are present in the cardiac
ventricles and valves, as well as in the arterial vascula-
ture. Case reports and small studies highlight several
potential cardiovascular complications, including heart
failure, valvular insufficiency, aortic aneurysms and dis-
section or rupture of large- and medium-sized blood
vessels. Inferential knowledge of potential cardiovascu-
lar complications of OI arises from other heritable dis-
orders of connective tissue, such as Marfan syndrome
(MFS) and vascular Ehlers-Danlos syndrome (vEDS).
This chapter will review the patterns of cardiovascu-
lar disease known to occur in people with OI and in
murine models of this condition, with additional review
of their pathophysiology (based on limited evidence to
date). Both medical and surgical therapies for cardio-
vascular disease in OI will also be reviewed.
HEART VALVE DISEASE
Several case reports describe aortic and mitral valve
regurgitation in the setting of OI, presumably due to
the inherent deficiency of type I collagens. Within neo-
natal mitral valves, collagen fibrils are highly organized
into tight bundles.
1
Among cardiac valves, left-sided
(mitral and aortic) insufficiency occurs more commonly
