Does brittle cornea syndrome have a bone fragility phenotype?

Abstract

Brittle cornea syndrome is a rare recessively inherited disorder (a sub-type of Ehlers-Danlos syndrome) with a clinical presentation dominated by corneal fragility and deafness. There have been suggestions that it may also have a bone fragility phenotype, but there has been little detailed description. We describe two siblings with brittle cornea syndrome due to compound heterozygous mutations in ZNF469 who had sustained ten or more fractures, the majority before the age of 15. When investigated as adults they had osteopenia, with lower z-scores than their parents who each carried one mutation. A bone biopsy from one sibling showed reduced cortical porosity. Both parents, who were heterozygous mutation carriers, had also suffered fractures but had normal bone density. This data supports the view that brittle cornea syndrome may have a bone fragility phenotype.