Familial retinal detachment associated with COL2A1 exon 2 and FZD4 mutations


  • Competing/conflicts of interest: No stated conflict of interest.

  • Funding sources: Centre for Eye Research Australia (CERA) receives Operational Infrastructure Support from the Victorian Government. We are grateful of the support provided by Peggy and Leslie Cranbourne Foundation. DAM is a recipient of the Pfizer Australia Senior Research Fellowship.

Professor David A Mackey, Lions Eye Institute, Centre for Ophthalmology and Visual Science, 2 Verdun Street, Nedlands 6009, Perth, Western Australia, Australia. Email: dmackey@utas.edu.au


Background:  To characterize the clinical and genetic abnormalities within two Australian pedigrees with high incidences of retinal detachment and visual disability.

Design:  Prospective review of two extended Australian pedigrees with high rates of retinal detachment.

Participants:  Twenty-two family members from two extended Australian pedigrees with high rates of retinal detachment were examined.

Methods:  A full ophthalmic history and examination were performed, and DNA was analysed by linkage analysis and mutation screening.

Main Outcome Measures:  Characterization of a causative hereditary gene mutation in each family.

Results:  All affected family members of one pedigree carried a C192A COL2A1 exon 2 mutation. None of the affected family members had early-onset arthritis, hearing abnormalities, abnormal clefting or facial features characteristic of classical Stickler syndrome. All affected members of the familial exudative vitreoretinopathy pedigree carried a 957delG FZD4 mutation.

Conclusions:  Patients with retinal detachment and a positive family history should be investigated for heritable conditions associated with retinal detachment such as Stickler syndrome and familial exudative vitreoretinopathy. The absence of non-ocular features of Stickler syndrome should raise the possibility of mutations in exon 2 of COL2A1. Similarly, late-onset familial exudative vitreoretinopathy may appear more like a rhegmatogenous detachment and not be correctly diagnosed. When a causative gene mutation is identified, cascade genetic screening of the family will facilitate genetic counselling and screening of high-risk relatives, allowing targeted management of the pre-detachment changes in affected patients.