Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers–Danlos syndrome (EDS VI): Report on 23 patients and review of the literature

Abstract

The brittle cornea syndrome (BCS) is a generalized connective tissue disorder characterized by corneal rupture following only minor trauma, keratoconus or keratoglobus, blue sclerae, hyperelasticity of the skin without excessive fragility, and hypermobility of the joints. It is inherited as an autosomal recessive trait but the underlying genetic defect remains undetermined. We present 23 patients (11 male) from 13 nuclear families followed at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, aged 3-28 years at last follow-up. A total of 28 events of corneal rupture were noted in 17 patients (eight male), among whom nine had had bilateral ruptures, and eight had had unilateral ruptures (four of the right cornea), while two had experienced re-rupture 2 and 4 years, respectively, after surgery; six patients (aged 3-21 years) had had no ruptures. We describe the natural history of our cases and discuss them together with those others reported in the literature. Because of similarities between the BCS and the kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VI), both disorders tend to have been confounded. Here, we show that all of our BCS patients tested in this regard had biochemical findings reflective of normal activity of lysyl hydroxylase, characteristically deficient in EDS VI, such as normal urinary total pyridinoline ratios and/or normal electrophoretic migration of collagen chains produced by dermal fibroblasts. The BCS is, therefore, an entity distinct from the kyphoscoliotic type of EDS, which has a much poorer prognosis. ß

Brittle Cornea Syndrome Associated with a Missense Mutation in the Zinc-Finger 469 Gene

“…In 31 of 60 patients with BCS, rupture of the cornea has been reported in 44 instances. 1 The left eyes of IV-4 and IV-6 were surgically repaired after corneal rupture, but then visual function was gradually lost. At present, the atrophic iris appears to be attached to the posterior surface of the cornea, and impaired drainage from the anterior chamber may have occurred.…”

“…Red hair is associated with BCS in some families, although only 10 of 60 patients with BCS have been reported to have red hair. 1 Most individuals with BCS have been born to consanguineous parents and are thus expected also to be homozygous for a chromosomal region adjacent to the BCS locus. Some of the nonocular features in patients with BCS could therefore be due to homozygosity for mutations in closely linked genes.…”

Presumed scleral perforation during forced duction testing of the superior oblique muscle

“…In this patient, ultrasound biomicroscopy revealed scleral thinning, a risk factor for scleral perforation during strabismus surgery. 7 Patients who may have thin sclera include those with high axial myopia, a history of previous scleritis, as in those with rheumatoid arthritis, 7 kyphoscoliosis type of Ehlers-Danlos syndrome, brittle cornea syndrome, 8 and buphthalmos. In such patients the forced duction test may be inadvisable.…”

A novel technique to treat traumatic corneal perforation in a case of presumed brittle cornea syndrome

“…3 A differential diagnosis is Ehlers-Danlos syndrome type VI, which is associated with kyphoscoliosis and thin sclera (with rupture after trivial trauma). It is characterised by the absence or mutation of the procollagen lysyl hydroxylase gene on chromosome 1, causing a deficiency of the enzyme lysyl-hydroxylase.…”