Brittle cornea syndrome

Alternate names

EDS VIB (formerly); Ehlers-Danlos syndrome type 6B (formerly); Fragilitas oculi with joint hyperextensibility; Corneal fragility, keratoglobus, blue sclerae, joint hyperextensibility; Dysgenesis mesodermalis corneae et sclerae

Definition

Brittle cornea syndrome (BCS) is a genetic disease involving the connective tissue in the eyes, ears, joints, and skin.

Causes and types

• There are 2 types of BCS.
• BCS type 1 is caused by changes (mutations) in the ZNF469 gene and BCS type 2 is caused by changes in the PRDM5 gene.

Inheritance

Autosomal recessive inheritance, a 25% chance

BCS is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this condition. People with BCS inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier
• While carriers of genetic diseases often do not have symptoms, carriers of BCS may have mild vision and musculoskeletal symptoms.
• Both corneal thinning and myopia have been reported in carriers.
• As such, a referral to an ophthalmologist is recommended for people who are known to be carriers of BCS or who may be at risk to be carriers.
• Screening for hip dysplasia may also be recommended.

Signs and symptoms

• The symptoms of brittle cornea syndrome (BCS) can vary, even among family members.
• The most common symptom is thinning of the cornea (keratoconus or keratoglobus) often leading to tearing and rupture after minor injury.
• This may occur as early as two years of age.
• The corneal thinning usually worsens over time.
• Scarring of the cornea may be found in areas where rupture has occurred.
• Other eye symptoms may include a blue tint to the sclera of the eye, myopia, and retinal detachment.
• Hearing loss may also occur and may be related to damage to the outer or middle ear (conductive hearing loss) and/or inner ear (sensorineural hearing loss).
• The hearing loss associated with BCS typically worsens over time.
• People with BCS may also experience musculoskeletal symptoms, including hip dysplasia and abnormal curvature of the spine (scoliosis).
• Other symptoms may include low muscle tone (hypotonia) in infancy, long and slender fingers and toes (arachnodactlyly), and above-average joint flexibility.
• People with BCS may also experience a tightening and shortening of muscles around the joints (contractures), particularly involving the pinky (small, fifth finger).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Corneal dystrophy
• High myopia(Severe near sightedness)
• Hyperextensible skin(Hyperelastic skin)
• Keratoglobus
• Soft skin

30%-79% of people have these symptoms

• Abnormality of hair pigmentation(Abnormality of hair color)
• Blue sclerae(Whites of eyes are a bluish-gray color)
• Bruising susceptibility(Bruise easily)
• Conductive hearing impairment(Conductive deafness)
• Corneal scarring
• Gait disturbance(Abnormal gait)
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Myalgia(Muscle pain)
• Osteoporosis
• Sensorineural hearing impairment
• Visual loss(Loss of vision)

5%-29% of people have these symptoms

• Abnormality of epiphysis morphology(Abnormal shape of end part of bone)
• Abnormality of the dentition(Abnormal dentition)
• Arachnodactyly(Long slender fingers)
• [[Camptodactyly ](Permanent flexion of the finger or toe)
• Cleft palate(Cleft roof of mouth)
• Corneal erosion(Damage to outer layer of the cornea of the eye)
• Flat cornea
• Glaucoma
• Hallux valgus(Bunion)
• Hernia
• Hip dysplasia
• Increased susceptibility to fractures(Abnormal susceptibility to fractures)
• Inguinal hernia
• Megalocornea(Enlarged cornea)
• Mitral valve prolapse
• Neonatal hypotonia(Low muscle tone, in neonatal onset)
• Pes planus(Flat feet)
• Pulmonic stenosis(Narrowing of pulmonic valve)
• Recurrent fractures(Increased fracture rate)
• Retinal detachment(Detached retina)
• Sclerocornea(Hardening of skin and connective tissue)
• Scoliosis
• Umbilical hernia

Diagnosis

The diagnosis of BCS is made based on symptoms and may be confirmed through genetic testing.

Treatment

• While there is no one treatment for BCS, certain measures to protect the eye and cornea may help prevent damage to the cornea, for example, use of special protective glasses.
• In instances of serious scarring and/or thinning, a corneal transplant or corneal graft may be attempted.
• While these procedures may not fully restore vision, they may help to avoid further corneal damage.
• Corneal cross-linking may also be an option to treat corneal thinning.
• This procedure involves using certain vitamins (B2) to try to strengthen the connective tissue in the cornea.
• Other symptoms including nearsightedness, retinal detachment, hearing loss, and problems in the musculoskeletal system are managed similarly to people with these concerns in the general population.

NIH genetic and rare disease info

• NIH info on Brittle cornea syndrome

Brittle cornea syndrome is a rare disease.

Brittle cornea syndrome Resources
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