Why does osteogenesis imperfecta cause blue sclera

The spectrum may range from almost asymptomatic patients with mild impact on stature, fractures, dentition and life span to patients with severe skeletal deformations, hearing loss, very short stature, dentinogenesis imperfecta and even perinatal mortality.

While the skeletal manifestations are more predominant, OI can also present with ocular complications such as blue sclera, hyperopic or myopic eyes, retinal detachments, decreased corneal rigidity, and glaucoma. In the United States, the prevalence of osteogenesis imperfecta is estimated to be 1 per 20, live births. While the disease is predominantly known to be autosomal dominant, inheritance is not always as clearly defined as de novo mutations may occur.

It is also important to note that mild forms of osteogenesis imperfecta may be underdiagnosed therefore actual prevalence may be higher. Prevalence worldwide is similar to the United States; however, there may be an increased risk of recessive forms of OI due to a higher likelihood of consanguinity. Osteogenesis imperfecta has no predisposition for a particular sex or race. Osteogenesis imperfecta is predominantly known as a bone disease that can also have systemic manifestations.

Blue sclera is the most commonly known ocular sign for osteogenesis imperfecta and it is caused by thin scleral collagen allowing the underlying darker choroid vasculature to be seen.

Patients with OI have shown a reduction in thickness of the corneal and scleral collagen fibers which can result in low ocular rigidity. OI patients may also have thin corneas, small corneal diameters, and keratoconus; however corneal ruptures are rare. Due to the significant impact of a corneal rupture or open globe, caution is always recommended in patients with connective tissue disorders, such as osteogenesis imperfecta.

These children had decreased central corneal thickness, decreased corneal resistance factor and had a corneal compensation IOP significantly higher in OI cases than in the control group.

Given this study, patients with OI should be monitored by an ophthalmologist for high IOP, development of glaucoma and other corneal pathologies. Type I collagen plays a significant role in the normal aqueous humor outflow and optic nerve function. It can be found in the trabecular meshwork TM , uveoscleral pathway and the optic nerve.

If there is a decrease in type I collagen in the TM, there can be an increase in the aqueous outflow resistance which can increase intraocular pressure. Similar effects would occur with decreased type I collagen in the uveoscleral pathway.

As type I collagen is also found in the optic nerve head and lamina cribosa, these regions combined with possible elevated IOP can result in the optic nerve being more susceptible to damage. In the recent report by Feinstein et al.

Of the patients that participated in the survey, the most common eye conditions were loss of vision and refractive errors. Ocular symptoms of OI can be life-changing and can cause permanent vision loss. Ophthalmologists should follow up with OI patients annually. Osteogenesis imperfecta is a polygenic disease that is most commonly inherited in an autosomal dominant pattern. COL1A1 gene is located at chromosome 17 at position Less commonly, OI can also occur due to autosomal recessive pattern of inheritance.

The pathophysiology of osteogenesis imperfecta is primarily due to a dysfunction in collagen and is classified under connective tissue diseases. Collagen is a necessary protein that provides strength to multiple tissues in the body. Type I collagen is specifically found in bone, cartilage, tendon, skin, and the many ocular tissues such as trabecular meshwork, optic nerve, sclera, and uveoscleral pathway. It is also the most abundant form of collagen in the body.

Collagen is created from procollagen, which is made of three chains. Triple stranded procollagen molecules are exported out of the cell and processed by multiple enzymes and cofactors to create the final mature collagen. Collagen strands then arrange themselves into long, thin fibrils with cross-linking to form a strong meshwork.

Therefore, poor procollagen formation yields an equally weak type I collagen to form throughout the body. Systemic examination was unremarkable except for the fracture olecranon process on the right side. Ophthalmic examination revealed bluish sclera Panel A involving the right eye Panel B as shown in Figure 1. His visual acuity, field of vision, color vision, pupillary reflexes, and extraocular movements were normal in both eyes. Skeletal survey and markers of bone metabolism were normal.

He was diagnosed as a case of idiopathic unilateral bluish sclera and was kept under follow-up. Bluish sclera is associated with osteogenesis imperfecta, Marfan's syndrome, Ehlers Danlos syndrome, Blue sclera syndrome Van der Heave syndrome , incontinentia pigmenti, and many other inherited conditions.

Unilateral bluish sclera is reported earlier with nevus depigmentosus, familial, and idiopathic in origin. The bluish sclera, therefore, is seen in many conditions with the defective type 1 collagen formation. Osteogenesis imperfecta is the classical condition associated with the bluish sclera.

However, our patient did not have any features to suggest the same. It is essential to screen for musculoskeletal and connective tissue abnormalities in patients with blue sclera.

Figure 1: Blue sclera Click here to view. Figure 2: Arms deformity Click here to view. Figure 3: Short legs Click here to view. Figure 4: X-ray shows arms deformity Click here to view.

This article has been cited by. Bilateral fractures of acetabulum in a young girl with osteogenesis imperfecta and epilepsy. Related articles Blue sclera fragile bone disease osteogenesis imperfecta. Access Statistics. Surgery also can correct dental problems from brittle teeth, and help with hearing problems. Bone breaks due to OI usually lessen in early adulthood, although they can start happening again later in life.

Taking steps to prevent fractures — along with early, ongoing medical care — will help most people with OI lead healthy, productive lives. Osteogenesis Imperfecta Brittle Bone Disease. Reviewed by: Michael B. Bober, MD. Larger text size Large text size Regular text size.

Signs of OI include: bones that break with no known cause or from very minor trauma bone pain bone deformity such as scoliosis or bowlegs a shorter stature brittle teeth called dentinogenesis imperfecta a blue, purple, or gray tint to the sclera the whites of the eyes triangular face shape hearing loss in adulthood loose joints What Are the Types of Osteogenesis Imperfecta OI?

Most cases of OI have symptoms that fall into one of these four classifications: Type I osteogenesis imperfecta — people with type I OI have less collagen than normal. They might also order tests like: X-rays , which can show fractures or healed breaks DNA tests , to identify the collagen gene mutation blood tests or urine tests , usually to make sure that other conditions, such as rickets, aren't causing the symptoms biochemical testing , which may include a skin sample to examine the collagen In severe cases, prenatal testing such as an ultrasound can detect fractures and bone deformities before a baby is born.

They can lower their risk of broken bones by: avoiding activities that put them at risk for a fall or collision, or put too much stress on the bones doing low-impact exercises such as swimming to build muscle strength and mobility and increase bone strength Handling Fractures When bones do break, it's important to treat them right away with casts, splints, and braces. Medicines Doctors might prescribe bone-strengthening medicines to increase bone density and further reduce the chances of fractures.

Surgery Sometimes, surgery is needed to repair a broken bone or fix a deformity. Looking Ahead Bone breaks due to OI usually lessen in early adulthood, although they can start happening again later in life.