BCS is a genetic connective tissue disorder that causes the cornea to be thin, fragile, and prone to rupture. BCS also causes blue sclerae and joint hypermobility.
Brittle Cornea Syndrome (BCS)
BCS is an ultra-rare disorder that affects less than 1 in 1 million people.
BCS is caused by differences in the genes called genetic variants. These genetic variants affect the connective tissue, which provides support, protection, and structure throughout the body.
BCS is caused by genetic variants of these genes:
- ZNF469
- PRDM5
BCS is inherited in an autosomal recessive pattern. This means if a person inherits the genetic variant from both of their parents, they will have BCS. People with one copy of the genetic variant are carriers of BCS. Carriers do not have BCS themselves, but some carriers of BCS do have eye problems. Carriers of BCS may pass the genetic variant on to their children.
BCS may be suspected if a person has:
- Corneal perforation (spontaneously or after minor trauma)
- Blue sclerae
- Joint hypermobility
- Kyphoscoliosis
- Developmental dysplasia of the hip
- Hearing loss
- Soft and/or translucent skin
If a person meets the diagnostic criteria for BCS, genetic testing should be done to confirm the diagnosis. Genetic testing is used to see if a person has the genetic variants that cause BCS.
To meet the diagnostic criteria for BCS, a person must meet:
- Major criterion 1 AND at least one other major criterion
OR
- Major criterion 1 AND at least three minor criteria
Major Criteria
- Thin cornea, with or without rupture (central corneal thickness often <400µm)
- Early onset progressive keratoconus
- Early onset progressive keratoglobus
- Blue sclerae
Minor Criteria
- Enucleation or corneal scarring as a result of previous rupture
- Progressive loss of corneal stromal depth, especially in central cornea
- High myopia, with normal or moderately increased axial length
- Retinal detachment
- Deafness, often with mixed conductive and sensorineural components, progressive, higher frequencies often more severely affected (“sloping” pure tone audiogram)
- Hypercompliant tympanic membranes
- Developmental dysplasia of the hip
- Hypotonia in infancy, usually mild if present
- Scoliosis
- Arachnodactyly
- Hypermobility of distal joints
- Pes planus, hallux valgus
- Mild contractures of fingers (especially 5th)
- Soft, velvety skin, translucent skin
BCS is managed by addressing the symptoms a person is experiencing. BCS can cause a variety of symptoms in many different areas of the body, so people with BCS may require multiple providers in different specialties to manage their care. Key aspects of care focus on preventing corneal rupture by wearing protective glasses, monitoring for vision and hearing issues, and managing other symptoms. Each person should work with their care team to develop a care plan that meets their individual needs.
