Brittle cornea syndrome: An heritable connective tissue disorder distinct from Ehlers-Danlos syndrome type VI and fragilitas oculi, with spontaneous perforations of the eye, blue sclerae, red hair, and normal collagen lysyl hydroxylation

Abstract

We report a patient with the characteristic features of the brittle cornea syndrome, a rare, autosomal recessively inherited disorder, namely brittle corneae, blue sclerae, and red hair. The patient also showed joint hyperextensibility, a soft skin, and dysplastic auricles with unusually soft cartilage. Phenotypically, the disorder bears a certain resemblance to fragilitas oculi and the type VI (ocular) form of the Ehlers-Danlos syndrome, two conditions which are, themselves, not readily distinguishable. However, the hydroxylysine content of dermal collagen was normal, as was the activity of lysyl hydroxylase in cultured dermal fibroblasts, thus supporting the distinction of the brittle cornea syndrome as an independent entity. No abnormality was discernible in types I or III collagens synthesised by cultured fibroblasts, but electron microscopy revealed dramatic ultrastructural alterations in dermis in that distributed over its whole thickness were 20-60 microns wide "holes" or fibre-free spaces, filled with an amorphous material.

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

“…5 Light microscopy of skin biopsies did not reveal any gross abnormalities of the architecture of the skin. We did not observe the "holes" in the dermis reported by Royce et al 8 Transmission electron microscopy revealed collagen fibrils in IV-4 to have a normal diameter. In IV-6, we observed minor variation in the diameter of the fibrils, and slightly thinner fibrils could be seen in some areas (data not shown).…”

“…In one report, 40-to 60-m holes were described in the dermis. 8 Other investigators have observed minor variation in collagen fibril diameter, 18 as seen in IV-6. In general, however, the morphology of the skin has been rather unremarkable with respect to both the gross architecture and the structure of the collagen fibrils.…”

Synthesis of prolyl 4-hydroxylase α subunit and type IV collagen in hemocytic granular cells of silkworm, Bombyx mori: Involvement of type IV collagen in self-defense reaction and metamorphosis

“…These cells were homogenized in the extraction buffer and the supernatants were used for determining the enzyme activity as previously reported (Royce et al, 1990). Recombinant baculoviruses (Ac3A1) containing human type III procollagen cDNA were prepared as reported previously (Tomita et al, 1995).…”

Etiology and Clinical Presentation of Astigmatism

“…The congenital form can be part of Ehlers-Danlos syndrome type Vl, or part of the corneal syndrome associated with blue sclera and red hair (Royce et al, 1990).…”