What is Brittle Cornea Syndrome (BCS)?
Brittle Cornea Syndrome (BCS) is a form of Ehlers-Danlos syndrome (EDS) characterised by the thinning of the cornea, the protective outer layer of the eye. This makes the cornea fragile and prone to ruptures, and may ultimately lead to blindness.
What causes BCS?
BCS is caused by mutations in either one of two genes: ZNF469 and PRDM5. ZNF649 encodes for a protein belonging to a family called zinc-finger proteins that are required to regulate the function of many other genes, including those involved in the production and organisation of collagen fibres that are important for the integrity of the eyes, skin, and other organs.
Like ZNF649, PRMD5 encodes for a gene regulator protein required for the synthesis and maintenance of collagen fibres and connective tissue components. Research has shown that mutations in this gene are implicated in several cases of BCS.
How is BCS inherited?
BCS is inherited in an autosomal recessive manner. Here, a person must inherit two defective copies of a gene — one from each parent — to develop the disease.
Those who inherit only one defective copy of the ZNF649 or PRMD5 gene are called carriers. Carriers of BCS also require medical attention; they are likely to show some symptoms of BCS, albeit to a milder extent than those diagnosed with the disease.
Signs & Symptoms of Brittle Cornea Syndrome
The symptoms of BCS can vary extensively even among members of the same family, and often overlap with those of another type of EDS known as Kyphoscoliotic EDS. The common clinical symptoms of BCS are summarised below:
Individuals with BCS develop a thin cornea known as keratoconus or keratoglobus as early as age 2. The cornea becomes more fragile over time, and can easily rupture even with a minor injury. Rupturing of the cornea can lead to scars in the eye that affect sight, and can cause blindness.
Patients may also show a blue tint to the sclera of the eye, nearsightedness (myopia), and retinal detachment.
BCS patients can also experience musculoskeletal disease symptoms, including scoliosis (abnormal sideways curvature of the spine), hip dysplasia (hip dislocation from birth or at a young age), hypotonia (muscle weakness), contractures (tightening of muscles near the joints), hypermobility of joints, and foot deformities. Some patients may also have arachnodactyly (long and slender fingers and toes).
BCS patients may also show soft, doughy skin along with hyperelasticity, but these symptoms are usually mild.
BCS patients may develop progressive hearing loss. Hearing loss can occur due to damage to the outer or middle ear (conductive hearing loss), and/or damage to the inner ear (sensorineural hearing loss).
Signs of Brittle Cornea Syndrome include:
- Soft skin
- Keratoglobus – corneal thinning
- Hyperextensible skin
- High myopia – severely near sighted
- Decreased corneal thickness
- Corneal dystrophy
- Visual loss
- Sensorineural hearing impairment
- Joint hyperflexibility
- Gait disturbance
- Easily bruised
- Blue sclerae – the whites of the eyes are a bluish-grey colour
Diagnosis of Brittle Cornea Syndrome
The diagnosis of BCS involves a detailed assessment of the patients’ medical history and that of their family members, along with a physical examination of the eyes, ears, muscles, and bones.
Since BCS is a genetic disease, genetic testing is typically required to confirm the presence of mutations in the ZNF649 or PRMD5 genes.
How is BCS treated?
Like other types of EDS, there is currently no cure for BCS. Existing treatments can help to manage symptoms and prevent them from worsening. Corneal rupture can be avoided by using protective, polycarbonate spectacles. Lifestyle changes may also need to be incorporated to further minimise the risks of corneal damage.
Studies have shown that a technique called collagen cross-linking, which involves the use of vitamin B2 (riboflavin) and ultraviolet light, can strengthen the cornea and improve vision in children.
Continuous monitoring and eye and ear exams are recommended for the early identification of problems.
Support for Brittle Cornea Syndrome
EDSNZ are working at compiling a list of resources of services and support you may be interested in. Among these are: