OMIM ID:
Brittle Cornea Syndrome 1
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This seems to be a subtype of the Ehlers-Danlos syndrome in which the ocular features are prominent. The cornea is thin and can perforate following relatively minor trauma. It is often misshapen as well resulting in keratoglobus and keratoconus. The external appearance can suggest buphthalmos but intraocular pressure is normal. The sclerae are bluish suggesting that the connective tissue defect is more widespread among eye tissues. The lens is not hypermobile, however. This disorder differs from Ehlers-Danlos type VIA (225400) (sometimes called the ocular-scoliotic form) in which there is a defect in lysyl hydroxylase although the ocular phenotype has some similarities.
Systemic Features
The skin is hyperelastic as in other forms of Ehlers-Danlos and the joints are hypermobile and are susceptible to dislocation. Some but not all cases reported from the Middle East have red hair and it has been suggested this may be part of the syndrome, at least in that part of the world.
Genetics
Inheritance
A mutation in the ZNF469 gene (16q24), encoding a defective zinc finger protein, is responsible for at least some cases of autosomal recessive brittle cornea syndrome. This confirms its identity as a unique type of connective tissue disease apart from other forms of Ehlers-Danlos in which ocular disease is present (such as type VIA in which the mutation is in the PLOD1 gene).
Homozygous mutations in PRDM5 (4q27) have been found in several families with brittle cornea syndrome 2 (614170).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.