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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 31  |  Issue : 3  |  Page : 221-224

Brittle cornea syndrome


Consultant Ophthalmologist, Dr. Rani Menon's Eye Clinic, Thrissur, Kerala, India

Date of Web Publication31-Dec-2019

Correspondence Address:
Dr. Rani Menon
Dr. Rani Menon's Eye Clinic, Thrissur, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_56_19

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  Abstract 


Brittle cornea syndrome is a rare generalized connective tissue disorder associated with extreme corneal thinning and other features such as blue sclera, keratoconus, keratoglobus, and high myopia. In this report, the mother and both the children had blue sclera of varying intensity along with corneal thinning in the children which was measurable only in the elder sibling.

Keywords: Blue sclera, brittle cornea, keratoconus, keratoglobus


How to cite this article:
Menon R, Menon SS. Brittle cornea syndrome. Kerala J Ophthalmol 2019;31:221-4

How to cite this URL:
Menon R, Menon SS. Brittle cornea syndrome. Kerala J Ophthalmol [serial online] 2019 [cited 2020 Jan 28];31:221-4. Available from: http://www.kjophthal.com/text.asp?2019/31/3/221/274586




  Introduction Top


Blue sclera with corneal fragility is an underrecognized ocular disorder. This case is reported due to its rarity and also to increase awareness to screen for associations at an early age and warn the patients about impending ocular risks.

Brittle cornea syndrome (BCS) is a rare autosomal recessive connective tissue disorder that presents with corneal thinning and fragility. Due to corneal thinning, they are predisposed to develop keratoglobus, keratoconus, high myopia, and irregular astigmatism.[1] Furthermore, in the later stages, they are prone to spontaneous corneal rupture, which leads to scarring and loss of vision in almost all of them affected by BCS.[2]


  Case reports Top


This is the case report of two siblings, sibling 1 is a 10-year-old girl and sibling 2 is a 4-year-old boy born of a nonconsanguineous marriage.

Case 1 (Sibling 1 – 10-year-old girl)

She was wearing glasses from the age of 6 years, for progressive defective vision. On examination, unaided visual acuity was 4/60 in the right eye and 2/60 in the left eye with best-corrected visual acuity of 6/36 in the right eye 6/18 in the left. Refraction readings were −3.75 sph − 5.75 cyl@13*(OD) and −6.5sph −1.25 cyl@169*(OS). Slit-lamp examination showed bluish discoloration of the sclera with globular cornea with extreme corneal thinning and protrusion both eyes. Corneal diameter was 12 mm both eyes.

The sclera was moderately blue [Figure 1].
Figure 1: Sclera was moderately blue

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Corneal topography by pentacam showed [Figure 2] extreme corneal thinning all around with thinnest pacymetry reading of 294 μm (OD) and 290 μm (OS).
Figure 2: Corneal topography by pentacam showed extreme corneal thinning all around with thinnest pachymetry reading of 294 μm (OD) and 290 μm (OS)

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Fundus examination was normal with a cup disc ratio of 0.4 both eyes. Periphery was also normal.

Intraocular pressures (IOPs) by Goldmann applanation tonometry at 2 pm was 20 mm in both eyes. Corrected IOP (after central corneal thickness [CCT]) was 32.5 mmHg (OD) and 32.75 mmHg (OS).

Optical coherence tomography (OCT) disc was normal with normal neuroretinal rim. OCT macula [Figure 3] showed normal foveal contour with macular thickness within normal limits.
Figure 3: Optical coherence tomography disc was normal with normal neuroretinal rim. Optical coherence tomography macula showed normal foveal contour with macular thickness within normal limits

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B scan was done to assess Retino Choroido Scleral (RCS) thickness and revealed RCS = 1.1 mm close to optic disc in both eyes, which was reduced.

Systemic examination was within normal limits for her age. No evidence of joint hyperextensibility or hearing loss.

Case 2 (Sibling 2 – 4-year-old boy)

He was brought for evaluation along with the elder sibling. Refraction −1.00 sph −2.5 cyl@15*(OD) and +2.00 sph −4.5cyl@163*(OS). Slit-lamp examination and fundus were within normal limits. Gross corneal thinning as in the elder sibling was not observed, but bluish discoloration of the sclera was more marked. [Figure 4] IOPs and topography could not obtained.
Figure 4: Sibling 2 (4-year-old boy)

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B scan shows RCS thickness = 1.13 mm

Parents –The mother has mild bluish discoloration of the sclera. [Figure 5] Corneal topography results were within normal limits. OCT disc and macula was also normal with corrected IOPs of 16 mm both eyes.
Figure 5: Mother has mild bluish discoloration of the sclera

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The mother denies any similar history in her two sisters and her parents. The father has no sclera discoloration, and CCT was also within normal limits.


  Discussion Top


BCS is a rare generalized connective tissue disorder associated with extreme corneal thinning and other features such as blue sclera, keratoconus, keratoglobus, and high myopia.[1] Extraocular manifestations include deafness, joint hypermobility, skin hyperelasticity, and developmental dysplasia of the hip.

Genetics

BCS results from mutation in one of the two genes, ZNF469, encoding zinc finger protein 469 and second PRMD5, encoding PR domain-containing protein 5.[3] Immunohistochemistry in eyes with BCS also found PRDM5 localisation in Bruch's membrane of retina apart from the corneal epithelium. Mutations in the ZNF469 gene are causative for BCS Type 1 and BCS Type 2 is caused by mutations in the PRDM5 gene.[4],[5] Mutations in ZNF469 gene are thought to be associated with changes in CCT. Recent researches also confirmed that ZNF469 also plays an important role in anterior segment development and hence in the pathogenesis of ocular disorders such as glaucoma.[6],[7] PRDM5 is found to be associated with extracellular matrix physiology.[8]

Ocular features

  1. Thin cornea (CCT often <400 μm); BCS corneas are unable to withstand normal biomechanical stresses and hence cannot maintain their structural integrity and shape, hence resulting in early-onset progressive keratoconus and/or keratoglobus, later leading onto corneal perforation and scarring
  2. Blue sclerae are usually present in those affected by BCS, but this is not universal,[9] may disappear over time, is also present in many individuals identified to be heterozygous carriers for BCS-associated mutations
  3. Secondary glaucoma has been reported in many affected patients, particularly those with extensive corneal damage following rupture
  4. Retinal detatchments have also been identified in few according to previous literature.[10]


Extraocular manifestations

Auditory features are less pronounced, but one-third of the patients have been found to have mixed sensineural and conductive hearing loss.[11]

Other musculoskeletal features observed were developmental dysplasia of hip, scoliosis, and small joint hypermobility and skin hyperelasticity.[4]

If there are no obvious extraocular features, extreme corneal thinning or spontaneous ocular rupture should be highly suspected for suspecting BCS.

Moreover, there exist some other diseases associated with brittle cornea and blue sclera such as the Ehlers–Danlos syndrome, osteogenesis imperfecta, and the Marfan syndrome.[12],[13]

However, patients with these diseases frequently have more pronounced generalized connective tissue manifestations as compared to more of ocular manifestations in BCS.

Treatment

Mainstay includes early diagnosis, preventing ocular rupture, and optimizing visual function. Providing protective polycarbonate spectacles can be beneficial to some extent in preventing direct trauma and rupture.

In cases of progressive BCS, epikeratoplasty (a partial thickness corneal graft) has been used in prevention of corneal rupture, which aims to increase the thickness of limbus to limbus and allow a penetrating keratoplasty subsequently [14] because of the extreme thinning and frailty, the corneas in BCS patients were not suitable for a corneal cross-linking procedure.[15]

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.
Ramappa M, Wilson ME, Rogers RC, Trivedi RH. Brittle cornea syndrome: A case report and comparison with Ehlers Danlos syndrome. J AAPOS 2014;18:509-11.  Back to cited text no. 1
    
2.
Avgitidou G, Siebelmann S, Bachmann B, Kohlhase J, Heindl LM, Cursiefen C. Brittle cornea syndrome: Case report with novel mutation in the PRDM5 gene and review of the literature. Case Rep Ophthalmol Med 2015;2015:637084.  Back to cited text no. 2
    
3.
Swierkowska J, Gajecka M. Genetic factors influencing the reduction of central corneal thickness in disorders affecting the eye. Ophthalmic Genet 2017;38:501-10.  Back to cited text no. 3
    
4.
Burkitt Wright EM, Porter LF, Spencer HL, Clayton-Smith J, Au L, Munier FL, et al. Brittle cornea syndrome: Recognition, molecular diagnosis and management. Orphanet J Rare Dis 2013;8:68.  Back to cited text no. 4
    
5.
Porter LF, Gallego-Pinazo R, Keeling CL, Kamieniorz M, Zoppi N, Colombi M, et al. Bruch's membrane abnormalities in PRDM5-related brittle cornea syndrome. Orphanet J Rare Dis 2015;10:145.  Back to cited text no. 5
    
6.
Lu Y, Dimasi DP, Hysi PG, Hewitt AW, Burdon KP, Toh T, et al. Common genetic variants near the brittle cornea syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. PLoS Genet 2010;6:e1000947.  Back to cited text no. 6
    
7.
Rohrbach M, Spencer HL, Porter LF, Burkitt-Wright EM, Bürer C, Janecke A, et al. ZNF469 frequently mutated in the brittle cornea syndrome (BCS) is a single exon gene possibly regulating the expression of several extracellular matrix components. Mol Genet Metab 2013;109:289-95.  Back to cited text no. 7
    
8.
Watanabe Y, Toyota M, Kondo Y, Suzuki H, Imai T, Ohe-Toyota M, et al. PRDM5 identified as a target of epigenetic silencing in colorectal and gastric cancer. Clin Cancer Res 2007;13:4786-94.  Back to cited text no. 8
    
9.
Khan AO, Aldahmesh MA, Alkuraya FS. Brittle cornea without clinically-evident extraocular findings in an adult harboring a novel homozygous ZNF469 mutation. Ophthalmic Genet 2012;33:257-9.  Back to cited text no. 9
    
10.
Christensen AE, Knappskog PM, Midtbø M, Gjesdal CG, Mengel-From J, Morling N, et al. Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene. Invest Ophthalmol Vis Sci 2010;51:47-52.  Back to cited text no. 10
    
11.
Al-Hussain H, Zeisberger SM, Huber PR, Giunta C, Steinmann B. Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI): Report on 23 patients and review of the literature. Am J Med Genet A 2004;124A: 28-34.  Back to cited text no. 11
    
12.
Biglan AW, Brown SI, Johnson BL. Keratoglobus and blue sclera. Am J Ophthalmol 1977;83:225-33.  Back to cited text no. 12
    
13.
Beighton P. Serious ophthalmological complications in the Ehlers-Danlos syndrome. Br J Ophthalmol 1970;54:263-8.  Back to cited text no. 13
    
14.
Kanellopoulos AJ, Pe LH. An alternative surgical procedure for the management of keratoglobus. Cornea 2005;24:1024-6.  Back to cited text no. 14
    
15.
Caporossi A, Mazzotta C, Baiocchi S, Caporossi T, Denaro R, Balestrazzi A. Riboflavin-UVA-induced corneal collagen cross-linking in pediatric patients. Cornea 2012;31:227-31.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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