Brittle Cornea Syndrome 1

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 [1] (225400 [2]) (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

A mutation in the ZNF469 [3] 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 [1] in which the mutation is in the PLOD1 [4] gene).

Homozygous mutations in PRDM5 [5] (4q27) have been found in several families with brittle cornea syndrome 2 [6] (614170 [7]).

Treatment

Treatment Options:

Treatment beyond corneal repair is limited.

References

Article Title:

Heterogeneous basis of the type VIB form of Ehlers-Danlos syndrome (EDS VIB) that is unrelated to decreased collagen lysyl hydroxylation [8]

Walker LC, Overstreet MA, Willing MC, Marini JC, Cabral WA, Pals G, Bristow J, Atsawasuwan P, Yamauchi M, Yeowell HN. Heterogeneous basis of the type VIB form of Ehlers-Danlos syndrome (EDS VIB) that is unrelated to decreased collagen lysyl hydroxylation. Am J Med Genet A. 2004 Dec 1;131(2):155-62.

PubMed ID:

15523625

Brittle cornea, blue sclera, and red hair syndrome (the brittle cornea syndrome) [9]

Ticho U, Ivry M, Merin S. Brittle cornea, blue sclera, and red hair syndrome (the brittle cornea syndrome). Br J Ophthalmol. 1980 Mar;64(3):175-7.

PubMed ID:

7387950

Ocular Ehlers-Danlos syndrome with normal lysyl hydroxylase activity [10]

Judisch GF, Waziri M, Krachmer JH. Ocular Ehlers-Danlos syndrome with normal lysyl hydroxylase activity. Arch Ophthalmol. 1976 Sep;94(9):1489-91.

PubMed ID:

962660