Brittle cornea syndrome (BCS) is a heritable connective tissue disorder that makes the cornea thin, fragile, and prone to rupture. BCS also causes symptoms in other areas of the body, including joint hypermobility and hearing loss.
BCS is an ultra-rare disorder that affects less than 1 in 1 million people.
Key signs and symptoms of BCS include:
You can learn more about the features of BCS by selecting different body parts from the menu below.
Genetic Basis
BCS is caused by genetic variants in these genes:
Humans have two copies of each gene because we inherit one from each parent. People with BCS typically have pathogenic variants in both copies of the ZNF46 or PRDM5 gene.
Inheritance
BCS is inherited in an autosomal recessive pattern. Autosomal means it can be passed on and inherited equally by males and females. Recessive means the condition only occurs when both copies of a gene are affected by pathogenic variants.
People with BCS will always pass on one pathogenic variant to their children. Their children will only have BCS if they inherit a second pathogenic variant in the same gene from their other parent.
People with one recessive pathogenic variant are known as carriers. Carriers do not have BCS themselves, but some carriers of BCS do have eye problems and joint hypermobility. Carriers of BCS may pass the genetic variant on to their children.
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 Criteria
Minor Criteria
BCS is managed by addressing the symptoms a person is experiencing. Key aspects of care focus on preventing corneal rupture by wearing protective glasses and avoiding injury, monitoring for vision and hearing issues, and managing other symptoms.
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. Each person should work with their care team to develop a care plan that meets their needs.
Signs and Symptoms
Eyes
Musculoskeletal
Spine
Skin
Cardiovascular
Chest and lungs
Gastrointestinal
Head
Ears
Hands
Feet
How to Use:
Explore the features of BCS by selecting different body parts from the menu. Please note that BCS affects each person differently. The symptoms listed here may not affect everyone with BCS, and people with BCS may have other symptoms that are not listed on this page. This page is intended to provide information about symptoms that may occur in individuals with BCS and does not constitute medical advice. Always consult a healthcare professional for personalized medical guidance.
Select from the list below to learn how BCS can affect the eyes.
The cornea is a clear protective dome that covers the iris and pupil and allows light to enter the eye. In BCS, the cornea is thinner than usual, with a central corneal thickness (CCT) of less than 220-450 μm (normal range 520-560 μm). This leaves the cornea more vulnerable to damage.
A corneal rupture is a partial or complete tear in the cornea. This may occur spontaneously or due to minor trauma in people with BCS. Corneal rupture often occurs in childhood in BCS and can lead to vision loss. Corneal rupture is a medical emergency. Rapid medical treatment is required to preserve vision.
The cornea is thin and vulnerable to damage in people with BCS. Damage to the cornea may result in corneal scarring, which can impair vision.
Some people with BCS lose their vision due to corneal rupture and scarring.
The cornea is a clear protective dome that covers the iris and pupil and allows light to enter the eye. Keratoconus is a condition that causes the cornea to gradually get thinner and bulge out into a cone shape. This can cause blurred vision and sensitivity to light.
Keratoglobus is a condition that causes the cornea to be thinner and bulge out into a globe shape. This can cause vision problems, including myopia and astigmatism.
The sclera (plural: sclerae) is a protective layer of connective tissue that surrounds most of the eye. It is usually white but is more transparent when collagen fibers are thin. This allows the underlying tissue to show through, giving the eyes a bluish color.
Myopia, also called nearsightedness or shortsightedness, is a condition that makes it difficult to see objects that are far away. Due to differences in eye shape, people with myopia can see objects near them more clearly but have trouble seeing objects further away.
Glaucoma is a condition that can lead to vision loss. Glaucoma occurs when the optic nerve is damaged, often due to increased pressure in the eye.
The cornea is a clear protective dome that covers the iris and pupil. A megalocornea is an enlarged cornea with a diameter of at least 13 mm.
The retina is a light-sensitive layer of tissue at the back of the eye. The retina senses light and sends signals to the brain that allow us to see. Retinal detachment occurs when the retina is pulled away from its normal position at the back of the eye.
Symptoms of retinal detachment include seeing many new floaters, sudden flashes of light, or a dark shadow or curtain covering part of the field of vision. Retinal detachment is a medical emergency. Rapid medical treatment is required to preserve vision.
Select from the list below to learn how BCS can affect the musculoskeletal system.
Joint hypermobility means a joint has a greater range of motion than usual. Many people with BCS have joint hypermobility, often in the hands and feet.
A joint is the point where two or more bones connect. Joint instability means the bones of a joint are not held in place securely. This can lead to joint subluxations, dislocations, sprains, and other injuries.
A joint dislocation occurs when the bones in a joint separate completely and are no longer touching. A subluxation is a partial dislocation in which a bone comes out of place but still touches the other bone(s) in the joint.
Congenital hip dysplasia, also called congenital hip dislocation, is a condition in which the hip joint is not formed correctly at birth. The hip is a ball-and-socket joint. The ball of the femur moves within the socket of the pelvis, allowing movement of the legs. In someone with hip dysplasia, the socket of the pelvis is too shallow to support the ball of the femur properly. This can lead to instability, pain, and problems with walking.
Muscle tone is the amount of tension (or resistance to movement) in the muscles. Muscle tone allows us to hold our bodies upright and affects the control, speed, and range of our movement. Muscle hypotonia, or low muscle tone, means the muscles are floppy and unable to properly support the body’s position and movement. It may require more effort for people with hypotonia to move and maintain good posture.
A joint contracture is a fixed tightening of tissues that prevents normal joint movement. Contractures of the fingers have been reported in some people with BCS, particularly in the pinky or 5th finger.
Bone density is the amount of minerals in the bones. Bones that contain more minerals are denser and stronger. Bones with less minerals are weaker and may be more vulnerable to fractures.
A bone fracture is a partial or complete break of a bone. Bone fractures are reported in some people with BCS but are not considered a common feature of the condition.
Select from the list below to learn how BCS can affect the spine.
Scoliosis is a sideways curve in the spine that gives the spine an “S” or “C” shape.
Kyphoscoliosis is a combination of two spinal conditions: kyphosis and scoliosis. Kyphosis is an abnormal forward curve in the spine that causes the upper back to look more rounded. Scoliosis is a sideways curve in the spine that gives the spine an “S” or “C” shape.
Select from the list below to learn how BCS can affect the skin.
Some people with BCS have soft, translucent skin, which can make their veins more visible. This may be harder to see on brown or black skin.
Skin hyperextensibility means the skin can be stretched beyond the normal range. Skin hyperextensibility is not a common feature of BCS but is reported in some people with the condition.
Some people with BCS bruise easily.
Wounds may heal more slowly than usual in some people with BCS.
Select from the list below to learn how BCS can affect the cardiovascular system.
The heart has four chambers separated by valves that open and close to ensure that blood flows in the correct direction. The mitral valve separates the left chambers of the heart. Mitral valve prolapse (MVP) occurs when the mitral valve is floppy and does not close tightly. MVP has been reported in some people with BCS but is not considered a common feature.
Select from the list below to learn how BCS can affect the chest and lungs.
Pectus excavatum is an indentation in the chest that occurs when the sternum grows inward. This happens when too much connective tissue grows between the ribs and the sternum. Mild pectus excavatum may not cause any problems, but if the indentation is deep enough, it can put pressure on the lungs and heart.
Select from the list below to learn how BCS can affect the gastrointestinal system.
A hernia occurs when an internal body part pushes through a weak spot in the tissues that support it, creating an outward bulge. Inguinal (groin) hernias have been reported in some people with BCS.
Select from the list below to learn how BCS can affect the head.
Some people with BCS have similar facial features, such as:
These features may be subtle and are not present in everyone with BCS.
Select from the list below to learn how BCS can affect the ears.
Some people with BCS have hearing loss, which may be conductive, sensorineural, or mixed.
Sensorineural hearing loss occurs when there is a problem with the inner ear or the auditory nerve that delivers sound to the brain.
Conductive hearing loss occurs when sound can’t reach the inner ear due to blockage, structural problems, or damage in the outer or middle ear.
Mixed hearing loss is a combination of sensorineural and conductive hearing loss.
Select from the list below to learn how BCS can affect the hands.
Some people with BCS have arachnodactyly, which means their fingers and toes are unusually long and slender.
Select from the list below to learn how BCS can affect the feet.
Flat feet (pes planus) means the feet have little to no arch when standing. When a person with flat feet stands, the entire bottom of their foot touches the ground.
A bunion (hallux valgus) is a bony bump at the base of the big toe. Bunions are reported in many people with BCS, often at an unusually early age.
Please note that BCS affects each person differently. The symptoms listed here may not affect everyone with BCS, and people with BCS may have other symptoms that are not listed on this page. This page is intended to provide information about symptoms that may occur in individuals with BCS and does not constitute medical advice. Always consult a healthcare professional for personalized medical guidance.
The Ehlers-Danlos Syndromes, Rare Types (Brady et al., 2017)
https://doi.org/10.1002/ajmg.c.31550
The 2017 International Classification of the Ehlers-Danlos Syndromes (Malfait et al., 2017)
https://doi.org/10.1002/ajmg.c.31552
More than meets the eye: Expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome (Dhooge et al., 2021)
https://doi.org/10.1002/humu.24199
Brittle cornea syndrome: recognition, molecular diagnosis and management (Burkitt Wright et al., 2013)
https://doi.org/10.1186/1750-1172-8-68
Brittle cornea syndrome: current perspectives (Walkden et al., 2019)
https://doi.org/10.2147%2FOPTH.S185287
