Rare Ophthalmology News

Disease Profile

Brittle cornea syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q79.6

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

EDS VIB (formerly); Ehlers-Danlos syndrome type 6B (formerly); Fragilitas oculi with joint hyperextensibility;

Categories

Congenital and Genetic Diseases; Eye diseases; Skin Diseases

Summary

Brittle cornea syndrome (BCS) is a genetic disease involving the connective tissue in the eyes, ears, joints, and skin. The symptoms of BCS typically involve thinning of the protective outer layer of the eye (cornea), which may lead to tearing or rupture after minor damage to the cornea. Other eye symptoms may include nearsightedness (myopia), a blueish tint in the white part of the eyes (blue sclera), and retinal detachment. Other symptoms may include hearing loss, abnormal positioning of the hip bones (hip dysplasia), and soft skin with abnormal scarring.[1] 

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. BCS is inherited in an autosomal recessive manner.[1][2][3] The diagnosis of BCS is made based on symptoms and may be confirmed through genetic testing. Management of BCS may include monitoring for vision loss, hearing loss, and the development of muscle or skeletal problems. Measures to prevent corneal rupture, such as wearing special protective glasses, may help delay vision loss. Other treatments may include corrective lenses (glasses), hearing aids, correcting hip dysplasia, and repairing retinal detachment.[1]

Symptoms

The symptoms of brittle cornea syndrome (BCS) can vary, even among family members.[1][3][2] 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).[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Corneal dystrophy
0001131
High myopia
Severe near sightedness
Severely close sighted
Severely near sighted

[ more ]

0011003
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin

[ more ]

0000974
Keratoglobus
0001119
Soft skin
0000977
30%-79% of people have these symptoms
Abnormality of hair pigmentation
Abnormality of hair color
0009887
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Corneal scarring
0000559
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Myalgia
Muscle pain
Muscle ache

[ more ]

0003326
Osteoporosis
0000939
Sensorineural hearing impairment
0000407
Visual loss
Loss of vision
Vision loss

[ more ]

0000572
5%-29% of people have these symptoms
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality

[ more ]

0000164
Arachnodactyly
Long slender fingers
Spider fingers

[ more ]

0001166
Camptodactyly
Permanent flexion of the finger or toe
0012385
Cleft palate
Cleft roof of mouth
0000175
Corneal erosion
Damage to outer layer of the cornea of the eye
0200020
Flat cornea
0007720
Glaucoma
0000501
Hallux valgus
Bunion
0001822
Hernia
0100790
Hip dysplasia
0001385
Increased susceptibility to fractures
Abnormal susceptibility to fractures
Bone fragility
Frequent broken bones
Increased bone fragility
Increased tendency to fractures

[ more ]

0002659
Inguinal hernia
0000023
Megalocornea
Enlarged cornea
0000485
Mitral valve prolapse
0001634
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Retinal detachment
Detached retina
0000541
Sclerocornea
Hardening of skin and connective tissue
0000647
Scoliosis
0002650
Umbilical hernia
0001537
Percent of people who have these symptoms is not available through HPO
Atypical scarring of skin
Atypical scarring
0000987
Autosomal recessive inheritance
0000007
Congenital hip dislocation
Dislocated hip since birth
0001374
Decreased corneal thickness
Thin cornea
0100689
Dentinogenesis imperfecta
0000703
Disproportionate tall stature
0001519
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Joint hypermobility
Double-Jointed
Flexible joints
Increased mobility of joints

[ more ]

0001382
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Keratoconus
Bulging cornea
0000563
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Molluscoid pseudotumors
0000993
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        Brittle cornea syndrome 1
        Brittle cornea syndrome 2
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Brittle cornea syndrome. Click on the link to view a sample search on this topic.

        Selected Full-Text Journal Articles

          References

          1. Burkitt Wright EM, Porter LF, Spencer HL, et al. Brittle cornea syndrome: recognition, molecular diagnosis and management. Orphanet J Rare Dis. May 4, 2013; 8(68):https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659006.
          2. Marla J. F. O'Neill. Brittle cornea syndrome 1; BCS1. Online Mendelian Inheritance in Man (OMIM). January 9, 2015; https://omim.org/entry/229200.
          3. Marla J. F. O'Neill. Brittle cornea syndrome 2; BCS2. Online Mendelian Inheritance in Man (OMIM). April 11, 2016; https://omim.org/entry/614170.
          4. Wan Q, Tang J, Han Y, Xiao Q, Deng Y. Brittle cornea syndrome: a case report and review of the literature. BMC Ophthalmol. September 18, 2018; 18(1):252. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142315.

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