Does brittle cornea syndrome have a bone fragility phenotype?

Area of Science:

• Genetics
• Ophthalmology
• Orthopedics

Background:

• Brittle cornea syndrome (BCS) is a rare, inherited disorder characterized by corneal fragility and hearing loss.
• Previous reports suggested a potential bone fragility phenotype, but detailed descriptions were lacking.

Observation:

• Two siblings with BCS, caused by ZNF469 mutations, experienced over ten fractures, mostly before age 15.
• Adult siblings exhibited osteopenia with lower bone mineral density Z-scores than their heterozygous parents.
• Bone biopsy in one sibling revealed reduced cortical porosity.

Findings:

• Compound heterozygous ZNF469 mutations are associated with significant bone fragility and osteopenia.
• Heterozygous carriers may also experience fractures, though bone density appears normal.

Implications:

• This study supports brittle cornea syndrome having a distinct bone fragility phenotype.
• Further research into ZNF469's role in bone health is warranted.
• Clinical evaluation for bone fragility should be considered in BCS patients.