Brittle Cornea Syndrome

Description

Brittle cornea, a form of Ehlers-Danlos syndrome, is a genetic disease which is caused by connective tissue changes in joints, skin, ears and eyes. Collagen is the most common protein in the human body and is responsible for holding connective tissue together. Brittle cornea syndrome is characterised by extreme thinning and increased fragility of the outer layer of the eye (cornea) which may lead to tearing or rupture with just minor injury, which can progress to blindness. People with Brittle cornea syndrome may also experience hearing loss, hip dysplasia, and joint hypermobility.

Symptoms

The symptoms of Brittle cornea syndrome can vary, even among affected family members. The onset of symptoms can occur as early as two years of age. The most common symptom associated with Brittle cornea syndrome is thinning of the cornea often resulting in tearing. The corneal thinning, sometimes referred to as keratoconus, often gets worse over time. Some people may experience scarring of the cornea where tears or ruptures have occurred, affecting their visual field. Other eye symptoms include a blue tint to the sclera (outer white part of the eye), myopia (nearsightedness), and retinal detachment.

Causes

Brittle cornea syndrome is a genetic condition. Two types of Brittle cornea syndrome are well described. Type 1 Brittle cornea syndrome is caused by genetic changes, called mutations, in the ZNF469 gene. Type 2 Brittle cornea syndrome is caused by mutations in the PRDM5 gene. Brittle cornea syndrome is inherited in an autosomal recessive manner. In this case, two copies of the disease causing gene need to be present, one of each are passed on by a mother and a father. It is possible that both parents do not have the condition themselves, but instead are carriers of the disease causing gene. More information on genetic inheritance patterns can be found here or contact the Fighting Blindness research department on 01 6789004 or e-mail research@fightingblindness.ie.

Diagnosis

Brittle cornea syndrome is diagnosed through a number of tests which are important for providing the correct diagnosis. These assessments will look at different symptoms such as motility and skin symptoms. The eye doctor will ask about a person’s medical history, including any family history of eye conditions. Individuals will receive a clinical eye examination where they may be asked to read letters off a chart (Snellen chart). They may also check intraocular pressure and examine visual field and visual acuity. An individual may receive a number of imaging tests. Optical coherence tomography (OCT) can also be used to assess the central corneal thickness which is commonly thinner accompanied by relative preservation of peripheral corneal thickness. As Brittle cornea syndrome is a genetic condition, a genetic test is also important to ensure the correct condition is diagnosed. In Ireland, this can be performed through the Target 5000 programme.

Genetic Diagnosis

It’s often impossible to tell which type of ocular condition a person has just by looking into the eye. As such, a genetic test may be necessary to confirm the diagnosis. The Target 5000 programme provides free genetic and clinical testing to all individuals living in Ireland with a genetic retinal degeneration, including BCM. Through genetic screening of the person awaiting diagnosis and their family members, the Target 5000 programme will provide more detailed information about the nature and inheritance pattern of the condition. As gene-specific clinical trials and treatments become available, knowing the genetic mutation associated with a genetic retinal degeneration will become even more important. Taking part in this programme ensures participants are included on a national registry from which participants can be identified for clinical trials and treatments and from which further information about each of the genetic retinal degenerations can be defined. For further information on the Target 5000 programme, please contact the Research Department on 01 6789004 or email research@fightingblindness.ie.

Treatment

At present, there is no treatment available for Brittle cornea syndrome, however there are significant research efforts underway which aim to change this. To find out more about these advances, please visit the ‘Latest Research’ section. Whilst there are no current treatments, certain protective measures could be taken to help prevent damage to the cornea, for example, use of special protective glasses. In instances where individuals have serious thinning or scarring of the cornea, a corneal transplant or corneal graft might be attempted. Corneal cross-linking (minimally invasive procedure to strengthen and stabilize the collagen fibres found in the cornea) may also be another method of treating thinning corneas. Other symptoms such as hearing loss, nearsightedness, and retinal detachment are managed similarly to people with these concerns in the general population. General eye check-ups are important for people living with BCM, as these individuals may still be at risk of developing other kinds of eye problems that affect the general population, some of which may be treatable. No matter what level of vision a person may have, it is important to look after the eyes. To find out more about what can be done to take care of the eyes on a daily basis, please visit our Tips for Good Eye Health. For further information, please contact the Research Department on 01 6789004 or email research@fightingblindness.ie.

Research

Great advances have been made with respect to understanding this condition, with much progress being made to develop therapies for it. Promising research exists with an aim to develop treatments for Brittle cornea syndrome, with a major focus on gene therapies. These gene therapies aim to deliver a “normal” copy of the gene which is mutated in this condition into the retina. As two genes are associated with the condition, ZNF469 (Type 1) and PRDM5 (Type 2), it makes this condition particularly suitable for gene therapy and a number of research efforts are investigating this. More information can be found on the clinical trials website where you can search by condition and location. Target 5000 research, largely funded by Fighting Blindness aims to determine the genetic cause and understand the nature of the condition over time. Through Target 5000, a national registry will also be developed which will greatly improve access to suitable clinical trials and treatments for people living in Ireland with BCM. For further information, please contact the Research Department on 01 6789004 or e-mail research@fightingblindness.ie. A study conducted by Professor Breandán Kennedy is investigating a group of neuroprotective drugs, known as HDAC inhibitors, for their potential to delay vision loss in retinal degenerations. This work seeks to identify new therapeutics which could provide significant benefit to individuals. To find out more about these studies, please contact the Research Department on 01 6789004 or e-mail research@fightingblindness.ie.

Supports

Receiving a diagnosis can be overwhelming for anyone, but this is not a journey that you have to make alone. There are many groups and resources available to provide support for people living with Stargardt Disease. Fighting Blindness offers a free and confidential counselling service (Insight Counselling). For further information please contact insight@fightingblindness.ie or call 01 6746496. We also offer support groups for people with a visual impairment to share their feelings and experiences with others facing the same challenges. Please consult the support groups section of our website here to access the latest timings and days for the various support groups we offer. For further information please contact insightgroups@fightingblindness.ie or call 01 6746496.

Resources

Féach provides support for parents of children living with sight loss in Ireland. ChildVision is the national education centre for children with sight loss in Ireland. Vision Ireland, formerly NCBI (National Council for the Blind in Ireland) provides support and services for people living with sight loss in Ireland. Irish Guide Dogs for the blind helps individuals and their families to achieve improved mobility and independence.