Familial retinal detachment associated with COL2A1 exon 2 and FZD4 mutations

AbstractBackground:  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.