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Open Access Research

Brittle cornea syndrome: recognition, molecular diagnosis and management

Emma MM Burkitt Wright12, Louise F Porter12, Helen L Spencer3, Jill Clayton-Smith12, Leon Au4, Francis L Munier5, Sarah Smithson6, Mohnish Suri7, Marianne Rohrbach8, Forbes DC Manson1 and Graeme CM Black12*

Author Affiliations

1 Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK

2 Genetic Medicine, St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK

3 University of Bristol Faculty of Medicine and Dentistry, Bristol Royal Infirmary, Bristol, UK

4 Royal Manchester Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK

5 Ophthalmology, Jules-Gonin Eye Hospital, Lausanne, Switzerland

6 Clinical Genetics, University Hospitals Bristol NHS Foundation Trust, Bristol, UK

7 Clinical Genetics Service, Nottingham University Hospitals NHS Trust, City Hospital Campus, Hucknall Road, Nottingham, NG5 1PB, UK

8 Division of Metabolism, Connective Tissue Unit, University Children's Hospital, Steinwiessstrasse 75, Zurich, 8032, Switzerland

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Orphanet Journal of Rare Diseases 2013, 8:68  doi:10.1186/1750-1172-8-68

Published: 4 May 2013

Abstract

Brittle cornea syndrome (BCS) is an autosomal recessive disorder characterised by extreme corneal thinning and fragility. Corneal rupture can therefore occur either spontaneously or following minimal trauma in affected patients. Two genes, ZNF469 and PRDM5, have now been identified, in which causative pathogenic mutations collectively account for the condition in nearly all patients with BCS ascertained to date. Therefore, effective molecular diagnosis is now available for affected patients, and those at risk of being heterozygous carriers for BCS. We have previously identified mutations in ZNF469 in 14 families (in addition to 6 reported by others in the literature), and in PRDM5 in 8 families (with 1 further family now published by others). Clinical features include extreme corneal thinning with rupture, high myopia, blue sclerae, deafness of mixed aetiology with hypercompliant tympanic membranes, and variable skeletal manifestations. Corneal rupture may be the presenting feature of BCS, and it is possible that this may be incorrectly attributed to non-accidental injury. Mainstays of management include the prevention of ocular rupture by provision of protective polycarbonate spectacles, careful monitoring of visual and auditory function, and assessment for skeletal complications such as developmental dysplasia of the hip. Effective management depends upon appropriate identification of affected individuals, which may be challenging given the phenotypic overlap of BCS with other connective tissue disorders.

Keywords:
Brittle cornea syndrome; Corneal rupture; Blue sclera; ZNF469; PRDM5