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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 29  |  Issue : 3  |  Page : 240-243

Blue sclera and osteogenesis imperfecta - A rare association


Department of Ophthalmology, Andaman and Nicobar Islands Institution of Medical Science, Port Blair, Andaman and Nicobar Islands, India

Date of Web Publication30-Jan-2018

Correspondence Address:
Dr. Sujit Das
Department of Ophthalmology, MS Ophthalmology, ANIIMS, Port Blair, Andaman and Nicobar Island, Islands
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_75_17

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  Abstract 


The sclera is a dense poorly vascularized connective tissue structure composed of Types I, III, IV, V, VI, and VIII collagen. The characteristic blue sclera is caused by thinness and transparency of the collagen fibers of the sclera that allow visualization of the underlying uvea. The sclera may be thinned in congenital diseases such as osteogenesis imperfecta or in acquired diseases such as iron deficiency anemia.

Keywords: Blue sclera, fragile bone disease, osteogenesis imperfecta


How to cite this article:
Das S, Bhatnagar K. Blue sclera and osteogenesis imperfecta - A rare association. Kerala J Ophthalmol 2017;29:240-3

How to cite this URL:
Das S, Bhatnagar K. Blue sclera and osteogenesis imperfecta - A rare association. Kerala J Ophthalmol [serial online] 2017 [cited 2018 May 25];29:240-3. Available from: http://www.kjophthal.com/text.asp?2017/29/3/240/224297




  Introduction Top


The sclera is a dense poorly vascularized connective tissue structure composed of Types I, III, IV, V, VI, and VIII collagen, as well as elastin, proteoglycans, and glycoproteins. The characteristic blue sclera is caused by thinness and transparency of the collagen fibers of the sclera that allow visualization of the underlying uvea. The sclera may be thinned in congenital diseases such as osteogenesis imperfecta (OI) or in acquired diseases such as iron deficiency anemia.[1] Severe forms are most often diagnosed early in life, but mild cases may not be noted until later in life. The blue-gray color of the sclera is due to the underlying choroidal veins which show through. This is due to the sclera being thinner than normal because the defective Type I collagen is not forming correctly.[2]

Epidemiology

In the United States, the incidence of OI is estimated to be one per 20,000 live births. An estimated 20,000-50,000 people are affected by OI in the United States.[3]

Pathophysiology

People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type I collagen. This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helix structure. As a result, the body may respond by hydrolyzing the improper collagen structure.[2] If the body does not destroy the improper collagen; the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness. As a genetic disorder, OI has historically been viewed as an autosomal dominant disorder of Type I collagen. Most cases have been caused by mutations in the COL1A1 and COL1A2 genes.[4] In the past several years, there has been the identification of autosomal recessive forms. At least seven subsets have been described although four major subtypes are most common and range from mild to severe. Individuals with Type I OI have little bone deformity, persistent blue sclera, near normal height by adulthood, and a >50% chance of hearing loss by adulthood. Patients with perinatal lethal (Type II) OI show the greatest severity, with multiple fractures in utero or from the delivery. These patients usually are stillborn or die early. The severity of OI depends on the specific gene defect. Most cases of OI are inherited from a parent. However, some cases are the result of new genetic mutations. A person with OI has a 50% chance of passing on the gene and the disease to his or her children.[4]

Symptoms

The fact that most of the children plus the mother have blue sclera should lead you to a genetic link. The findings of developmental delay, iron deficiency, and dental caries and one child's history of a fracture should lead you to review the various presentations of OI. All people with OI have weak bones, and fractures are more likely. People with OI often have short stature because of their compressive leg fractures. However, the severity of the disease varies greatly.

The classic symptoms include:

  • Blue tint to the whites of their eyes (blue sclera)
  • Multiple bone fractures
  • Early hearing loss (deafness).


Because Type I collagen is also found in ligaments, people with OI often have loose joints (hypermobility) and flat feet. Symptoms of more severe forms of OI may include:

  • Bowed legs and arms
  • Kyphosis
  • Scoliosis (S-curve spine).


Exams and tests

OI is most often suspected in children whose bones break with very little force. A physical exam may show that the whites of their eyes have a blue tint. A definitive diagnosis may be made using a skin punch biopsy. Family members may be given a DNA blood test. If there is a family history of OI, chorionic villus sampling may be done during pregnancy to determine if the baby has the condition. However, because so many different mutations can cause OI, some forms cannot be diagnosed with a genetic test. The severe form of Type II OI can be seen on ultrasound when the fetus is as young as 16 weeks.

Possible complications

Complications are largely based on the type of OI present.[1]

  • Hearing loss (common in Type I and Type III)
  • Heart failure (Type II)
  • Respiratory problems and pneumonia due to chest wall deformities
  • Spinal cord or brain stem problems
  • Permanent deformity.


Outlook (prognosis)

How well a person does depends on the type of OI they have.

  • Type I, or mild OI, is the most common form. People with this type can live a normal lifespan [1]
  • Type II is a severe form that often leads to death in the first year of life
  • Type III is also called severe OI. People with this type have many fractures starting very early in life and can have severe bone deformities. Many people need to use a wheelchair and often have a somewhat shortened life expectancy [1]
  • Type IV, or moderately severe OI, is similar to Type I, although people with Type IV often need braces or crutches to walk. Life expectancy is normal or near normal.


Treatment

There is not yet a cure for this disease.[5] However, specific therapies can reduce the pain and complications from OI. Drugs that can increase the strength and density of bone are called bisphosphonates. Low-impact exercises, such as swimming, keep muscles strong and help maintain strong bones. People with OI can benefit from these exercises and should be encouraged to do them.[5] In more severe cases, surgery to place metal rods into the long bones of the legs may be considered.[6] This procedure can strengthen the bone and reduce the risk for fracture. Bracing can also be helpful for some people. Surgery may be needed to correct any deformities. This treatment is important because deformities (such as bowed legs or a spinal problem) can interfere with a person's ability to move or walk.

Prevention

Genetic counseling is recommended for couples considering pregnancy if there is a personal or family history of this condition.[7]


  Case Report Top


A 32 years old male patient of Andaman & Nicobar Island reported to our OPD with an enquiry of his blue colouration of both eyes and whether this will transmitted to his next generation or not if married. On history he had it since his childhood without associate with any visual complaints, hearing defect, any bony pain except for bony deformity of both hands. He had short legs after an accidental fall from a height of 15 feet at the age of 8 years old. On enquiry there was a compressive fracture of both legs. There was no associated blue sclera running in the family. On examination his best corrected (BCVA) was 6/6 in both eyes; intraocular pressure in both eyes was 15 mmHg. On anterior segment examination lids were normal, extra ocular movements was normal, there was blue sclera in eyes [Figure 1], cornea, conjunctiva and lens was normal. On dilated eye examination fundus was normal. On systemic examination he had bow arms [Figure 2], short legs [Figure 3], no spinal cord and chest deformity. X-ray both hands shows arm deformity [Figure 4]. There was no gait abnormality. This patient was then sent to orthopaedic OPD for further evaluation.
Figure 1: Blue sclera

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Figure 2: Arms deformity

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Figure 3: Short legs

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Figure 4: X-ray shows arms deformity

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  Discission Top


The sclera is a dense poorly vascularized connective tissue structure composed of Types I, III, IV, V, VI, and VIII collagen, as well as elastin, proteoglycans, and glycoproteins. The characteristic blue sclera is caused by thinness and transparency of the collagen fibers of the sclera that allow visualization of the underlying uvea. The sclera may be thinned in congenital diseases such as OI or in acquired diseases such as iron deficiency anemia.[1] Severe forms are most often diagnosed early in life, but mild cases may not be noted until later in life. People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type I collagen.[7] This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helix structure. The relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered in OI, causing brittleness of bones. As a genetic disorder, OI has historically been viewed as an autosomal dominant disorder of Type I collagen. Most cases have been caused by mutations in the COL1A1 and COL1A2 genes.[2] Diseases associated with blue sclera includes multiple connective tissue disorders, such as Marfan syndrome, Ehlers–Danlos syndrome, OI, pseudoxanthoma elasticum, and Willems De Vries syndrome, to name a few. Bone and blood disorders also on the list include Diamond–Blackfan anemia, severe iron deficiency anemia, Juvenile Paget's disease, and acid phosphatase deficiency.[3]

Most cases of OI are inherited from a parent. However, some cases are the result of new genetic mutations. A person with OI has a 50% chance of passing on the gene and the disease to his or her children. Prognosis depends on the type of disease – Type I is the most common and have normal life expectancy, whereas Types II–IV are severe one.[7] Still now, there is no cure of this disease. Genetic counseling is recommended for couples considering pregnancy if there is a personal or family history of this condition.


  Conclusion Top


Blue sclera may be associated with multisystem disorders so good history taking is most important. Most dreaded complication associated are OI, cardiac abnormalities, and hearing defects. Osteogenesis imperfecta is a autosomal disorder, and genetic counseling is recommended for couples considering pregnancy if there is a personal or family history of this condition.[8] Patients should have multidisciplinary approach to prevent complications as so far no cure of this disorder.[6]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet 2004;363:1377-85.   Back to cited text no. 1
    
2.
Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, et al. Type V osteogenesis imperfecta: A new form of brittle bone disease. J Bone Miner Res 2000;15:1650-8.  Back to cited text no. 2
    
3.
Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 1998;339:947-52.  Back to cited text no. 3
    
4.
Kelly M, Evelyn B. Encyclopedia of Human Genetics and Diseases. J Bone Miner Res 2014;27:1524-30.  Back to cited text no. 4
    
5.
Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. J Bone Miner Res 2012;14:1645-48.  Back to cited text no. 5
    
6.
Harrington J, Sochett E, Howard A. Update on the evaluation and treatment of osteogenesis imperfecta. Pediatr Clin North Am 2014;61:1243-57.  Back to cited text no. 6
    
7.
Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979;16:101-16.  Back to cited text no. 7
    
8.
Shapiro JR, Lietman C, Grover M, Lu JT, Nagamani SC, Dawson BC, et al. Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation. J Bone Miner Res 2013;28:1523-30.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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